Novel 5-nitro-imidazole antimicrobially effective compounds

ABSTRACT

5-Nitro-imidazoles of the formula   WHEREIN X is hydrocarbon or a free or esterified hydroxy group; Y and Z each are H or, collectively, a bridging group consisting of -CH2- and/or one of O, S, SO and SO2, -CH2CH2-, or -CHAwherein A is -CH3, -C2H5 or -C6H5; R1 and R2 each are alkyl, halogen or free, esterified or etherified -OH; and R3 is H, alkyl, substituted alkyl, halogen, free, esterified or etherified -OH, amino, amido or aminoalkoxy; have antibacterial and antifungal activity, particularly against protozoa and especially against Trichomonas vaginalis.

United States Patent 91 Ruler et al.

]March 20, 1973 [54] NOVEL S-NITRO-IMIDAZOLE ANTIMICROBIALLY EFFECTIVECOMPOUNDS [75] Inventors: Clemens Ruler; Rudolf Albrecht; Hans-JoachimKessler; Eberhard Schroder, all of Berlin, Germany [73] Assignee:Schering Aktiengesellschafl, Berlin,

' Germany [22] Filed: July 8, 1970 [21] Appl. No.: 53,298

[30] Foreign Application Priority Data July 10, 1969 Germany ..P 19 35685.5

[52] US. Cl ..260/240 J, 424/248, 424/250, 424/273, 260/240 A, 260/247.7E, 260/268 [51] Int. Cl. ..C07d 49/36 [58] Field of Search.....260/240J, 309, 240 R, 240 A [5 6] References Cited UNITED STATES PATENTSFOREIGN PATENTS OR APPLICATIONS Chretien et al. ..260/240 J Asato et a1..260/240 D l1/l965 Japan .Q, ..260/240 A OTHER PUBLICATIONS Corvaiser,Bull. Soc. Chim. France 1962, pages 528 to Albrecht et al., Annalen DerChemie, vol. 736, pages 110 to 125 (June 1970) Hubbal et al., J. Chem.Soc., 1929, pages 21 to 32 Primary ExaminerJohn D. RandolphAttorney-Millen, Raptes & White [57] ABSTRACT S-Nitro-imidazoles of theformula vaginalis.

47 Claims, No Drawings NOVEL S-NITRO-IMIDAZOLE ANTIMICROBIALLY EFFECTIVECOMPOUNDS BACKGROUND OF THE INVENTION This invention relates to novel5-nitro-imidazoles.

The effectiveness of nitroimidazoles against trichomonads has been knownsince the discovery of the antibiotic azamycin (2-nitroimidazole, S.Nakamura and H. Umezawa, J. Antibiotics (Tokyo), 9 A, 66 10 [1955]).However, these and other. 2-nitroimidazoles have proved to be ofrelatively limited usefulness. See G. C. Lancini, E. Lazzari, R.Pallanea, ll Farmaco Ed. Sc." 2 l 278 1966). As the best among a largenumber of synthesized compounds (C. Cosar, Arzneimittelforschung" [DrugResearch] 16, 23 H9661), only the commercial preparation metronidazole(I-(Z-hydroxyethyl)-2-methyl-5-nitroimidazole; see, e.g., French Pat.No. 1,212,028) has evolved from the 5- nitroimidazoles.

It has now been found that the condensation products as defined hereinof the l-substituted 5-nitro- 2-imidazo1yl aldehydes with ketonescontaining active methylene groups exhibit a far stronger activityagainst Trichomonas vaginalis than metronidazole. Moreover, they exhibitantibacterial and antifungal effectiveness and are also active againstother protozoa.

SUMMARY OF THE INVENTION The compounds of this invention can berepresented by the formula wherein X is a saturated or unsaturatedhydrocarbon group containing one to five carbon atoms or free oresterified Z-hydroxyethyl group;

Y and Z each are hydrogen atoms or, collectively, a ring-forming (a) CH(b) one of O, S, SO and --SO (c) a combination of (a) and (b), (d) CH CHor (e) CHA wherein A is CH C H or -C H R R and R each are H, alkylcontaining one to five carbon atoms, halogen, or a free, esterified oretherified hydroxy group; and, additionally, R can be the correspondingalkyl substituted in the terminal position by halogen or a free,esterified or etherified hydroxy group as defined herein, or a primary,secondary or tertiary amino or aminoalkoxy group or an amido group, andthe acid addition salts and the quaternary ammonium salts thereof.

DETAILED DISCUSSION In the compounds of Formula I, X can be saturated orunsaturated. Examples of X which are saturated hydrocarbon are methyl,ethyl, isopropyl, butyl, sec.- butyl, iso-butyl, tert.-butyl, hexyl,heptyl, octyl, nonyl and decyl. Examples of unsaturated hydrocarbon areethenyl, ethynyl, allyl, propynyl, l-methylallyl, crotyl, butadienyl,2-octenyl, 6-octenyl, etc. Preferred are those containing l-4 carbonatoms and a single unsaturation, preferably a double bond in theB-position.

When X is a 2-hydroxyethyl group in the compounds of this invention, theOH group can be free or esterified to form a benzoyloxyethyl or analkanoyloxyethyl group of the formula alkyl COOCH CH containing one tofive carbon atoms in the alkyl group.

Y and Z can each be a hydrogen atom, or collectively, a bridging,ring-forming group containing one or In the compounds of this inventionR,, R and R each can be H, an alkyl group of one to five carbon atoms asillustrated above for X, halogen, viz., Cl, Br, I or F, or a free,esterified or etherified OH group. Additionally, R can be a primary,secondary or tertiary amino, amido, aminoalkoxy or amidoalkoxy group.

When R, or R is an etherified ---OH group, the ether group can be alkoxycontaining one to five carbon atoms, e.g., methoxy, ethoxy, propoxy,isopropoxy, butoxy, tertiary-butoxy, amyloxy, and the like or otherether group as illustrated hereinafter for R When R or R is anesterified OH group, the ester group can be an acyloxy group of theformula alkyl COO containing one to five carbon atoms in the alkyl groupor other esterified hydroxy group illustrated hereinafter for R When Ris an esterified hydroxy group, the ester group can be an ester of analiphatic or aromatic carboxylic or sulfonic acid containing one to 10carbon atoms, such as, for example, acetic acid, butyric acid, benzoicacid, cinnamic acid, methanesulfonic acid, ptoluenesulfonic acid, orbutane-sulfonic acid.

Other examples of esterified hydroxy R groups are those in which theester group is acyloxy wherein the acyl group is the acyl radical of,for example, a loweraliphatic acid, e.g., formic, propionic, butyric,isobutyric, valeric, isovaleric, trimethylacetic, 2-methylbutyric,3-ethylbutyric, hexanoic, diethylacetic, triethylacetic, heptanoic,octanoic, a-ethylisovaleric, acyclic acid, e.g., cyclopropylideneacetiq,a cycloaliphatic acid, e.g., cyclopentylformic, cyclopentylacetic,B-cyclopentylpropionic, cyclohexylformic, cyclohexylacetic,Bwyclohexylpropionic, an aryl or alkaryl acid, e.g., 2, 3, or4-methylbenzoic, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethylbenzoic,ethylbenzoic, 2,4,6-trimethylbenzoic, 3-methyl-a-naphthoic, an aralkylacid, e.g., phenylacetic, phenylpropionic, a dibasic acid, e.g.,succinic, glutaric, a-methylglutaric, B- methylglutaric,B,B-dimethylglutaric, adipic, pimelic, suberic, a hydroxy acid, e.g.,glycolic, lactic, citric, tartaric, d-maleic, d-glyceric, mannonic,gluconic, salicylic, an amino acid, e.g., glycine, diglycollamic,triglycollamic, methylglycine, dimethylglycine, diethylglycine,para-aminosalicylic, para-aminobenzoic, other heretosubstituted acids,e.g., ethylmercaptoacetic, benzylmercaptoacetic, cyannoacetic,chloroacetic, fluoroacetic, trichloroacetic, trifluoroacetic,thioglycolic, 2,3 ,4-trimeth0xybenzoic a-naphthoxyacetic,B-pyrrolidylpropionic, carbamic acids, e.g., carbamic acid,phenylcarbamic, n-butylcarbamic,

dimethylcarbamic, diethylcarbamic, allophanic, or a heterocyclic acid,e.g., B-furylcarboxylic, N-methylpyrrolidyl-2-carboxylic, a-picolinic,indole-2-carboxylic,

6-hydroxyindolyl-3-acetic, N-methylmorpholyl-Z-carboxylic andpyrrolyl-2-carboxylic acid.

Other examples of esterified R --OH groups in which the ester is asulfonyloxy group are those in which the sulfonyl group is arylsulfonyl,e.g., benzenesulfonyl, m,m'-dimethylbenzenesulfonyl,o,odimethylbenzenesulfonyl, sym.-trimethylbenzenesulfonyl,sym.-triethylbenzenesulfonyl, m-ethylbenzenesulfonyl,para-isopropylbenzenesulfonyl, m-n-butylbenzenesulfonyl, or isalkylsulfonyl, e.g., ethylsulfonyl, propylsulfonyl, isopropylsulfonyl,butylsulfonyl, ten.- butylsulfonyl, isoamylsulfonyl, hexylsulfonyl,heptylsulfonyl, octylsulfonyl, or heterocyclic sulfonyl, e.g.,apyridinesulfonyl, a-pyrane-sulfonyl, a-thiophenesulfonyl,a-furansulfonyl, a-tetrahydrofuransulfonyl, or other alkyl-,carbocyclic' and heterocyclic aryl-, alkaryland aralkyl-sulfonyl group,preferably one containing 1-8 carbon atoms and -2, preferably Ol N, S orO hetero atoms, which are preferably ring carbon atoms, in theheterocyclic ring (R group).'

When R is an etherified hydroxy group, the etherifying group can bealkyl containing one to five carbon atoms, e.g., methyl, ethyl, propyl,isopropyl, butyl, isobutyl, tert.-butyl, iso-amyl and amyl, alkenyl,e.g., allyl or aralkyl, e.g., benzyl.

In the compounds of this invention R, can also be a primary, secondaryor tertiary amino group or aminoalkoxy group.

Preferred N-substituted amino groups are monoand dialkylamino groupswherein each alkyl group contains one to five carbon atoms, e.g.,methylamino, ethylamino, -n-propylamino, isopropylamino, butylamino,isobutylamino, amylamino, dimethylamino, methylethylamino, diethylamino,methyl-npropylamino, dipropylamino, diisopropylamino,methyl-isobutylamino, di-n-butylamino and methylamylamino.

Other examples of substituted amino are those wherein the amino nitrogenatom is mono-substituted or disubstituted with saturated hydrocarbonother than alkyl, or unsaturated hydrocarbon, containing one to fivecarbon atoms or, together with the N-atom, forms a heterocyclicaminosubstituent containing, e.g., four to 14, preferably four to six carbonatoms and one to three, preferably one or two heteroatoms including theamino nitrogen atom and zero to three, preferably zero to one rings,which substituent can be substituted by one or more alkyl groups of oneto five carbon atoms, and contain a N-, O- or S-atom in addition to theamino nitrogen atom as a ring member, e.g., pyrrolidino, 2-methylpyrrolidino, 2,5-dimethylpyrrolidino, 3-ethylpyrrolidino,piperidino, homopiperidino, morpholino, imidazole, triazole, tetrazole,oxazole, dioxazole, isothiazole, pyridazine, pyrimidine, piperazine,isoxazine, morpholine, indole, benzoxazine, anilino, N-lower-alkylanilino, benzylamino, N-lower-alkylbenzylamino, o-toluidino,p-toluidino and N-loweralkyl-phenylethylamino.

R can also be a corresponding amido group, e.g., an acylated orsulfonylated amino group, e.g., wherein the acyl or sulfonyl group isacetyl-, propi0nyl-, butyryl-, methanesulfonyl-, benzenesulfonyl-,toluenesulfonyl or other acyl or sulfonyl group as defined hereinabove.

R, can also be an aminoalkoxy group wherein the alkoxy group containstwo to five carbon atoms,

preferably two, and the amino group is a primary, secondary or tertiaryamino group as defined above.

Preferred of the N-substituted aminoalkoxy groups are saturated andunsaturated rn'onoand dialkylaminoethoxy, free and esterified monoanddihydroxyalkyl )-aminoethoxy, monoand di-( acyloxyalkyl)-aminoethoxy,monoand dicycloalkylaminoethoxy, pyrrolidinoethoxy, piperidinoethoxy,hexa-, octa, and decamethyleniminoethoxy, piperazinoethoxy, andmorpholinoethoxy wherein the alkyl groups contain one to five carbonatoms and the cycloalkyl group contains five or six carbon atoms. Thecyclic-amino groups can be substituted on a ring carbon atom and the N'-amino nitrogen atom, in the case of the piperazine ring, by alkyl,hydroxy, acyloxy, acyl, hydroxyalkyl, or acyloxyalkyl containing one tofive carbon atoms in the alkyl and/or acyl groups, and can be bridgeddirectly or via an alkylene group.

The following are preferred classes of compounds of this inventiondefined by Formula I:

a. X alkyl containing one to four carbon atoms, preferably CH b. Xallyl,

c. Y and Z are -CH i.e., l-indanones;

d. Y and Z are -CH CH i.e., l-tetralones;

e. Y and Z are 0, i.e., 3-benzofuranones;

f. Y and Z are Cl-l S-, i.e., 4-thiachromanones;

g. Y and Z are H, i.e., acetophenones;

h. at least one, preferably one or two of R R and R are H;

i. one or two of R R and R is H and the remainder are free, esterifiedor etherified hydroxy, preferably wherein any esterified hydroxy isacetoxy and any etherified hydroxy is lower-alkoxy, especially methoxy,or B-terL-aminoethoxy, B-hydroxyethoxy or B-acyloxyethoxy;

j. combinations of(c), (d), (e), (f) and (g) with one or both of (a) and(h) or (i);

k. pharmaceutically acceptable, i.e., physiologically acceptable, acidaddition salts of each of the above classes of compounds, especiallyhydrochlorides.

The compounds of this invention are preferably isolated and administeredin the form of an acid addition salt, e.g., inorganic acids, includinghydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid,phosphoric acid, organic acids, including lactic acid, acetic acid,propionic acid, citric acid, benzoic acid, succinic acid, heptagluconicacid, etc. Preferred are the pharmaceutically acceptable acid additionsalts, i.e., those formed with acids which do not materially increasethe toxicity of the free base form thereof. However, acid addition saltsof toxic acids, e.g., perchloric, picric, etc., can be used forisolation, purification and/or characterization purposes and are alsoembraced within the scope of this invention.

Quaternary ammonium salts of the compounds of this invention formed byreaction with e.g., an alkyl halide, aralkyl halide, dialkyl sulfate,alkyl sulfonate, preferably lower-alkyl halides, also possess activityagainst trichomonas vaginalis and are included within the scope of thisinvention. When a compound of this invention possesses two basic aminogroups, obviously the quaternary ammonium form of both amino groups canbe formed. Examples of quaternary ammonium groups are trimethylammoniumiodide, trimethylammonium sulfate, ethyldimethylammonium bromide,benzyldimethylammonium chloride, N-methyl-pyrrolidinium iodide andother, e.g., lower-alkyl ammonium chlorides, bromides, iodides andsulfates of the free base form of the compounds of this inventiondescribed in the examples which follow.

The novel compounds can be prepared by the following methods:

(a) An aldehyde of the formula OzNKiCHO wherein X has the values givenabove, or a functional derivative of the aldehyde, is reacted with acompound of the formula III wherein X, Y, Z, R,, R and R have the valuesgiven above, is nitrated;

(c) a product of (a) or (b) when Y and Z collectively are a ring-forming-S0, -SO SOCH SO -CH CH SO-, or CH -SO -bridge, is produced by oxidizinga compound of the formula W R1 f wherein X and R R and R have the valuesgiven above and D represents one of the groups S, S CH and CH -S, so asto convert the thio group to a sulfoxide or sulfonyl compound.

The process according to (a) can be conducted at room temperature or atan elevated temperature in a acidic reaction medium, preferably in theanhydride of an aliphatic carboxylic acid of l-5 carbon atoms or inglacial acetic acid in the presence of concentrated sulfuric acid. Thecondensation can also be conducted in HCl-containing ethanol, in formicacid, in orthophosphoric acid, and in piperidine/glacial acetic acid.Any acylation of hydroxyl groups or amino groups occurring during thereaction can, if desired, be reversed by saponification. On the otherhand, the preparation of acylated products can be conducted by effectingthe condensation in the presence of the anhydride of the acid desiredfor the acylation when the acid is aliphatic and contains 1-6 carbonatoms, or by reacting free hydroxyl or amino groups with thecorresponding acid chloride and anhydride, respectively. Products inwhich R is an aminoalkoxy group can also i be obtained by reacting thecorresponding tosyloxy or halogen compound of Formula I with an amine,the halogen compounds preferably being prepared from the correspondinghydroxyl compounds with halogenating agents, such as, for example,thionyl chloride or bromide. I

The salt formation of the compounds containing amino groups can likewisebe conducted subsequently, as in process (a).

Preferred functional derivatives of the starting aldehydes (II) are thediacetates.

The nitration according to process (b) can be conducted in accordancewith the conventional methods, for example, with nitric acid inconcentrated sulfuric acid or in the presence of the BF N O complex.Process (b) generally, gives less satisfactory results than process (a).

The oxidation of the sulfur atom, according to process (c), to thesulfoxide or sulfone can be conducted, for example, with hydrogenperoxide or an organic peracid.

The novel compounds exhibit good antibacterial and antifungal effectsand are especially effective against protozoa and, among the latter,specifically effective against Trichomonas vaginalis. Table 1illustrates the superior effect of the compounds of this inventionagainst Trichomonas vaginalis, compared to the conventional commercialpreparation metronidazole used in trichomoniasis. (This compound isdescribed in French Pat. No. 1,212,028, published on Mar. 21, 1960. Withrespect to the effectiveness of this compound and numerous other5-nitroimidazoles, none of which was more active than the former, see C.Cosar, Arzneimittelforschung [Drug Research] 16, 23 [1966]).

TABLE 1 Minimum Inhibitory Concentration in Compound ylml. AgainstTrichamonas vaginalis 6,7-Dimethoxy-2-( S-nitrol-methyl-2- The toxicityof the compounds of this invention is low, as evidenced by the fact theyare well tolerated by mice upon an oral administration of 1 g./kg.

The compounds of Formula I are useful in the treatment of Trichomonasvaginalis infections. For such use, they can be formulated intoconventional drug forms with the additives, carrier substances, andflavoring agents customary in pharmaceutical preparations which do notdeleteriously react with the effective agents, employing conventionalmethods. For oral application, particularly suitable are tablets,dragees, capsules, pills, suspensions and solutions. Such compositionscan employ, for example, water, alcohol, polyethylene glycols, gelatin,sucrose, lactose, amylose in solutions and suspensions and magnesiumstearate, talc, starch, sugars, etc., in tablets. The concentration ofthe effective agent in the thus-formulated compositions is dependent onthe activity of the specific compound employed, the responsiveness ofthe individual patient and the mode of administration.

Tablets usually contain, for example, 0.1 0.5 g. of

effective agent and 0.1 5 g. of a pharmacologically inactive excipient.

For topical application, the compounds of this invention can be appliedas a powder, solution suspension, foam or aerosol or as vaginal tabletsand suppositories. For parenteral application, aqueous or oily solutionsor suspensions can be used.

In the following examples, the temperatures are set forth in degreescentigrade.

Without further elaboration, it is believed that one skilled in the artcan, using the preceding description, utilize the present invention toits fullest extent. The following preferred specific embodiments are,therefore, to be construed as merely illustrative, and not limitative ofthe remainder of the disclosure in any way whatsoever.

EXAMPLE 1 405 mg. (2.5 millimols) of S-methoxy-l-indanone, 388 mg. (2.5mmol) of S-nitro-1-methyl-2-imidazolyl aldehyde, and 350 mg. ofanhydrous sodium'acetate were allowed to stand in 2.5 ml. of aceticanhydride for 90 minutes at 70 C. After cooling to 50, vacuum-filtering,and washing with water, as well as digesting in boiling ethanol, 235 mg.(32 percent of theory) of 5- methoxy-2-( S-nitrol-methyl-2-imidazolylmethylene)- l -indanone was obtained, m.p. 256258.

C H N Calculated: 60.19 4.38 14.04 Found: 60.44 4.22 13.94

EXAMPLE 2 81 mg. (0.5 mmol) of 5-methoxy-1-indanone and 78 mg. (0.5mmol) of S-nitro-I-methyl-Z-imidazolyl aldehyde were boiled in 2 ml. of75 percent aqueous ethanol with 0.05 ml. of concentrated hydrochloricacid for 3 hours. After cooling to 20 and working the reaction mixtureup as described in Example 1, 10 mg. (6.8 percent of theory) of5-methoxy-2-(5-nitro-lmethy1-2-imidazoly1methy1ene)-1-indanone wasobtained.

EXAMPLE 3 81 mg. (0.5 mmol) of S-methoxy-l-indanone and 78 mg. (0.5mmol) of v5-nitro-1-methyl-2-imidazolyl aldehyde were boiled for 1 hourin 1 ml. of formic acid. After cooling to 20 and working up the reactionmixture as described in Example 1, 15 mg. (10 percent of theory) ofS-methoxy-Z-(S-nitro-1-methy1-2 imidazolyl-methylene)- 1 -indanone wasobtained.

EXAMPLE 4 81 mg. (0.5 mmol) of S-methoxy-l-indanone and 78 mg. (0.5mmol) of S-nitro-l-methyl-2-imidazolyl aldehyde were allowed to standfor 2 days at 20 in 3.5 ml. of benzene with l l p.l. of piperidine and 9,ul. of glacial acetic acid; then, the reaction mixture wasvacuum-filtered and worked up as set forth in Example 1, thus obtaining7 mg. (5 percent of theory) of 5-methoxy-2-(5-nitro-1-methyl-2-imidazo1ylmethylene l -indanone.

EXAMPLE 5 388 mg. (2.5 mmol) of S-nitro-1methyl-2-imidazolyl aldehydeand 350 mg. of anhydrous sodium acetate were allowed to stand in 2.5 ml.of acetic anhydride for 90 minutes at 100. The reaction mixture wascooled, vacuum-filtered, and washed with 5 ml. of water. Afterrecrystallization, 125 mg. (19 percent of theory) of 5-nitro-l-methyl-2-diacetoxymethyhimidazole was obtained, m.p. 144l46.

81 mg. (0.5 mmol) of S-methoxy-l-indanone and 128 mg. (0.5 mmol) of5-nitro-1-methy1-2-diacetoxymethyl-imidazole, as well as mg. ofanhydrous sodium acetate were reacted in 0.5 ml. of acetic anhydride, asdescribed in Example 1, and worked up, thus obtaining 240 mg. (33percent of theory) of 5'-methoxy-2-(5-nitro-1-methyl-2imidazolyl-methylene)-l-indanone.

EXAMPLE 6 330 mg. of indanone was reacted and worked up as described inExample I, thus obtaining 322 mg. (48 percent of theory) of2-(5-nitro-l-methyl-2-imidazolylmethylene 1 -indanone, m.p. 250-254 C HN Calculated: 62.44 4.12 15.60 Found: 62.27 4.39 15.80

EXAMPLE 7 440 mg. of S-ethoxy-l-indanone, 388 mg. ofS-nitrol-methyl-2-imidazolyl aldehyde, and 350 mg. of anhydrous sodiumacetate were allowed to stand in 2.5 ml. of acetic anhydride for minutesat a temperature of After cooling to 5, vacuum-filtering, washing withwater, and digesting with tetrahydrofuran, 182 mg. (23 percent oftheory) of5-ethoxy-2-(5-nitro-lmethyl-2-imidazolyl-methylene)-l-indanone wasobtained, m.p. 261265.

C H N Calculated: 61.33 4.83 13.41 Found: 61.76 4.86 13.54

EXAMPLE 8 510 mg. of 5-butoxy-2-indanone was reacted and worked up asdescribed in Example 7, thus obtaining 259 mg. (30 percent of theory) of5-butoxy-2-(5-nitro- 1 -methy1-2-imidazo1yl-methylene)- 1 -indanone,m.p. 243-246.

C H N Calculated: 63.32 5.62 12.31 Found: 63.87 5.95 12.69

EXAMPLE 9 370 mg. of S-hydroxy-l-indanone was reacted as described inExample 7. The crude product was recrystallized from dimethylformamide,thus obtaining 324 mg. (40 percent of theory of 5-acetoxy-2-(5-nitro-1-methyl-2-imidazo1yl-methy1ene 1 -inda.none, m.p. 244-248.

C H N Calculated: 58.71 4.01 12.84 Found: 59.02 4.20 13.04

EXAMPLE 10 370 mg. of 4-hydroxy-1-indanone was reacted as set forth inExample 7. The crude product was digested with methanol, thus obtaining540 mg. (67 percent of theory) of4-acetoxy-2-(5-nitro-1methy1-2-imidazo1ylmethy1ene)-1-indanone, m.p.241243;

c H N Calculated: 58.71 4.01 12.84 Found: 58.70 3.95 13.03

EXAMPLE 11 540 mg. (1.65 mmol) of4-acetoxy-2-(5-nitro-lmethyI-Z-imidazolyl-methylene 1 -indanone wasboiled for 2 hours in 13.5 ml. of ethanol with 6.8 ml. of concentratedhydrochloric acid. The reaction mixture was cooled, vacuum-filtered, andrecrystallized from dimethylformamide, thus obtaining 276 mg. (59percent theory) of 4-hydroxy-2-(5-nitro-1-methy1-2-imidazo1yl-rnethylene)- l-indanone; m.p. 285287.

C H N Calculated: 58.94 3.89 14.73 Found: 59.17 4.00 14.77

EXAMPLE 12 480 mg. of 4,5-dimethoxy-l-indanne was reacted and worked upas described in Example 7, thus obtaining 425 mg. (52 percent of theory)of 4,5-dimethoxy-2- -nitro- 1 -methy1-2-imidazolyl-methylene l-indanone;m.p. 228-230.

c H N Calculated: 58.36 4.60 12.76 Found: 58.37 4.42 12.71

EXAMPLE 13 365 mg. of 6-methyl-1-indanone was reacted as set forth inExample 7. The crude product was recrystallized from a mixture ofacetonitrile-chloroform- 10 tetrahydrofuran, 25:30:10. 133 mg. (19percent of 455 mg. of 5-methoxy-6-hydroxy-l-indanone was reacted asdescribed in Example 7. The crude product was digested with methanol andrecrystallized from dimethylformamide, thus obtaining 260 mg. (30percent of theory) of5-methoxy-6-acet0xy-2-(5-nitro-lmethyl-Z-imidazolyl-methylene)l-indanone. Melting point: 248-252.

C H N Calculated: 57.14 4.24 1 1.76 Found: 57.45 4.17 1 1.78

EXAMPLE 15 5 90 mg. of 5-methoxy-6-acetoxy-2-(S-nitro-1-methyl-2-imidazo1yl-methy1ene)-1-indanone was reacted and worked up asdescribed in Example 11, thus obtaining 396 mg. (76 percent of theory)of 5- methoxy-6-hydroxy-2-( S-nitro-1-methy1-2-imidazo1ylmethylene)-1-indanone, m.p. 290.

Calculated: 57.14 4.16 13.33

Found: 57.76 4.25 13.46

EXAMPLE 16 415 mg. of 6-chlor0-1-indanone was reacted as set forth inExample 7. The crude product was digested with acetonitrile, thusobtaining 431 mg. (57 percent of theory) of6-ch1oro-2-(5-nitro-1-methy1-2-imidazoly1- methylene 1 -indanone; m.p.'25 8-259.

C H N Calculated: 55.36 3.34 13.83 Found: 54.76 3.35 14.12

EXAMPLE 17 540 mg. of 5-acetoxy-2-( S-nitrol -methyl-2-imidazo1y1-methylene)-l-indanone was reacted and worked up as describedin Example 1 1, thus obtaining 420 mg. percent of theory) of5-hydroxy-2-(5- nitro 1 -methy1-2-imidazolyl-methylene 1 -indanone; m.p.292.

' C H Calculated 58.94 3.89 Found: 58.38 4.19

EXAMPLE 18 370 mg. of 7-hydroxy-l-indanone was reacted as set forth inExample 7. The crude product was recrystallized .from a mixture ofacetonitrile-chloroform, 1:1, thus obtaining 180 mg. (22 percent oftheory) of 7- acetoxy-2-(5-nitro-l-methyl-2-imidazolyl-methylene)-1-indanone;m.p. 225229.

Calculated: 58.94 3.89 Found: 58.38 4.19

EXAMPLE 19 485 mg. of 7-acetoxy-l-indanone was reacted as described inExample 7. The crude product was digested with methanol, thus obtaining80 mg. 10 percent of theory) of 7-acetoxy-2-(5-nitro-l-methyl-2-imidazolyl-methylene 1 -indanone.

EXAMPLE 20 550 mg. of 2-ethoxyethoxy)-1-indanone was reacted and workedup as described in Example 7; thus obtaining 100 mg. (1 1 percent oftheory) of 5-(2- ethoxyethoxy )-2-(S-nitrol-methyl-2-imidazolylmethylene )-1-indanone, m.p. 220222.

Calculated 60.49 5.36 1 1.76

Found: 59.91 5.50 1 1.56

EXAMPLE 21 365 mg. of 3-methy1-1-indanone was reacted and worked up asset forth in Example 7, thus obtaining 100 mg. (14'percent of theory) of3-methyl-2-(5-nitro-1- rnethyl-Z-imidazolyl-methylene)-l-indanone, m.p.215-216.

Found: 63.83 4.62 14.94

EXAMPLE 22 C N Calculated: 54.71 3.37 12.76 Found: 54.22 3.40 12.78

EXAMPLE 23 542 mg. of 6-acetoxy-2-( 5-nitrol -methyl-2-imidazolyl-methylene)-3-benzofuranone was reacted and worked up as setforth in Example 1 1, thus obtaining 207 mg. (44 percent of theory) of6-hydroxy-2-(5- nitro-1-methyl-2-imidazolyl-methylene)-3-benz0fu ranone,m.p. 290.

C H N Calculated: 54.36 3.16 14.63 Found: $3.86 3.38 14.70

EXAMPLE 24 350 mg. of thioindoxyl was reacted as described in Example 7.The crude product was digested with dimethylformamide, thus obtaining132 mg. (18 percent of, theory) of2-(5-nitro-1-methy1-2-imidazolylmethylene)-thioindoxyl; m.p. 283288.

c H N 5 Calculated: 54.36 3.16 14.62 11.16

Found: 54.56 3.47 14.30 1 1.50

EXAMPLE 25 541 mg. of 7-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-l-indanone was reacted as set forth in Example 1l. The crude product was digested with ethanol, thus obtaining 271 mg.(97 percent of theory) of 7-hydroxy-2-(5-nitrol-methyl-2-imidazolylmethylene)- l -indanone; m.p. 265268.

C H N Calculated: 58.94 3.89 14.73 Found: 59.32 3.85 14.69

EXAMPLE 26 365 mg. of 4-methyl-1-indanone was reacted as described inExample 7. After digesting in hot dimethylformamide, 213 mg. (30 percentof theory) of 4-methyl-2-(5-nitro-l-methyl-2-imidazolylmethylene)- 1-indan0ne was obtained; m.p. 245-255.

c H N Calculated: 63.59 4.63 14.83 Found: 63.73 4.80 14.58

EXAMPLE 27 435 mg. of 6-isopropyl-l-indanone was reacted and worked upas described in Example 26, thus obtaining 242 mg. of6-isopropyl-2-(5-nitro-l-methyl-2- imidazoly1-methylene)-l-indanone (31percent of theory); m.p. 243/50255.

c 11 N 01161116166: 65.59 5.51 13.50 Found: 65.50 5.67 13.46

EXAMPLE 28 407 mg. of 4-methoxy-l-indanone was reacted and worked up asdescribed in Example 26, thus obtaining 209 mg. (28 percent of theory)of 4-methoxy-2-(5- nitro- 1-methyl 2-imidazolyl-methylene)-1-indanone;

C H N Calculated: 60.19 4.38 14.04 Found: 60.00 4.50 13.93

EXAMPLE 29 470 mg. of 5-allyloxy-l-indanone was reacted and worked up asdescribed in Example 26, thus obtaining 176 mg. (22 percent of theory)of 5-allyloxy-2-(5- nitro- 1 -methyl-2-imidazolyl-methy1ene l -indanonem.p. 256260.

C H N Calculated: 62.76 4.65 12.92 Found: 62.89 4.61 12.95

EXAMPLE 30 594 mg. of S-benzoxy-l-indanone was reacted and worked up asset forth in Example 26, thus obtaining 159 mg. (17 percent of theory)of 5-benzoxy-2-(5- nitro-1-methyl-2-imidazoly1-methylene)-1-indanone;m.p. 256260.

C H N Calculated: 67.20 4.57 l 1.21 Found: 67.25 4.86 1 1.20

EXAMPLE 31 415 mg. of 4ch1oro-1-indanone was reacted and worked up asdescribed in Example 26, thus producing 166 mg. (22 percent of theory)of 4chloro-2-(5-nitro- 1 -m ethyl-2-imidazolyl-methylene)- 1 -indanone,m.p. 239 /44 B249.

C H N Calculated: 55.36 3.34 13.83 Found: 55.29 3.24 13.84

EXAMPLE 32 480 mg. of 5,6-dimethoxy-l-indanone was reacted and worked upas set forth in Example 26, thus obtaining 180 mg. (22 percent oftheory) of 5,6-dimethoxy-2- (S-nitrol -methyl-2-imidazolyl-methylene l-indanone; m.p. 258-266. 25

C H N Calculated: 58.36 4.60 12.76 Found: 58.10 4.70 13.00

EXAMPLE 33 455 mg. of 5-hydroxy-6-methoxy-l-indanone was reacted andworked up as described in Example 26, thus obtaining 118 mg. (13 percentof theory) of 6- 35 methoxy-S -acetoxy-2-( S-nitrol-methyl-2-imidazolylmethylene l -indanone; m.p. 258-259.

C H N Calculated: 57.14 4.24 1 1.76 Found: 57.00 4.64 1 1.78

EXAMPLE 34 590 mg. of6-methoxy-5-acetoxy-2-(5-nitro-lmethyl-2-imidazolyl-methylene 1-indanone was reacted as set forth in Example 1 1. Aftervacuum-filtering, 475 mg. (91 percent of theory) of 5-hydroxy-6-methoxy-2-(5-nitro-l-methyl-2-imidazolylmethylene)-l-indanone wasobtained, m.p. 290.

C H N Calculated: 63.59 4.63 14.83 Found: 63.73 4.80 14.58

EXAMPLE 35 455 mg. of 4-chloro-7-hydroxy-l-indanone was reacted andworked up as set forth in Example 26, thus producing 292 mg. (32 percentof theory) of 4-chloro- 7-acetoxy-2-(5-nitro-1-methyl-2-imidazolylmethylene )-1-indanone, m.p. 24 l242.

C H N Calculated: 53.12, 3.35 1 1.62 Found: 52.64 3.36 11.78

EXAMPLE 36 600 mg. of 4-chloro-7-acetoxy-2-(S-nitrol -methyl-2-imidazolyl-methylene)-l-indanone was reacted as described in Example11. After vacuum-filtering, 530 mg. (99 percent of theory) of4-chloro-7-hydroxy-2-(5- nitro- 1-methyl-2-irnidazo1yl-methylene)- l-indanone was obtained, m.p. 266-267.

Calculated: 52.59 3.16 13.14

Found: 52.80 3.17 13.20

EXAMPLE 37 Calculated: 69.75 4.10 12.21

Found: 69.00 4.74 12.01

EXAMPLE 38 485 mg. of 6,7-dimethoxy-3-benzofuranone was reacted andworked up as described in Example 26, thus producing 231 mg. (28 percentof theory) of 6,7- dimethoxy-2-( 5-nitrol -methyl-2-irnidazolylmethylene)-3-benzofuranone, m.p. 25 3/826 1 Calculated: 54.38 3.96 12.69 Found:54.16 4.00 12.50

EXAMPLE 39 370 mg. of 4-chromanone was reacted as set forth in Example7. After digesting in hot dimethylfonnamide and recrystallizing fromtetrahydrofuran, 10 mg. (1.4 percent of theory) of 3-(5-nitrol-methyl-2-imidazolylmethylene )-4-chromanone was obtained, m.p. 215-218.

c 11 N Calculated: 58.94 3.89 14.73 Found: 58.70 4.00 14.48

EXAMPLE 40 410 mg. of 7-hydroxy-4-chromanone was reacted as described inExample 7. After the addition of 5 ml. of water, the reaction mixturewas cooled to 5", the precipitated product was vacuum-filtered andrecrystallized from dimethylformarnidelwater. 78 mg. (9.2 percent oftheory) of7-acetoxy-3-(5-nitro-lmethyl-2-imidazolyl-methylene)-4-chromanone wasobtained, m.p. 202203.

C H N Calculated: 55.65 4.38 12.17 Found: 56.75 3.89 [2.31

EXAMPLE 41 388 mg. (2.5 mmol) of S-nitro-1-methy1-2-imidazolyl aldehydeand 440 mg. (2.5 mmol) of 6-methoxy-1- tetralone were heated in 2.55 ml.of glacial acetic acid and 0.055 ml. of 95 percent Sulfuric acid for 6hours to 100. After cooling, the reaction liquor was mixed with methanoland vacuum-filtered, thus obtaining 154 mg. (20 percent of theory) of6-methoxy-2-(5-nitro-1- methyl-2-imidazoly1-methylene 1 -tetralone, m.p.2 1

C H N Calculated: 61.33 4.83 13.41 Found: 61.45 5.20 13.27

EXAMPLE 42 v415 mg. of 5-chloro-1-indanone was reacted and worked up asdescribed in Example 26, thus producing 20 mg. (2 percent of theory) of5-chloro-2-(5-nitro-lmethy1-2-imidazolyl-methylene l -indanone, m.p.266/74B276.

H N Calculated: 55.36 3.34 13.83 Found: 55.44 3.31 13.75

EXAMPLE 43 570 mg. (2 mmol) of 5-hydroxy-2-(5-nitro-l-methyl-2-imidazolyl-methylene)-l-indanone was agitated for 1 hour at 20 with660 mg. (4 mmol) of cinnamic acid of ethanol, vacuum-filtering of theprecipitate, and recrystallization from dimethylformamide, 632 mg. (76percent of theory) of5-cinnamoy1oxy-2-(5-nitro-lmethyl-2-imidazolyl-methylene)-l-indanone wasobtained; m.p. 252 254.

c H N Calculated: 66.50 4.13 10.12 Found: 66.20 4.46 10.20

EXAMPLE 44 485 mg. (2.5 mmol) of 7-methoxy-4- thiachromanone was reactedand worked up as described in Example 41, thus obtaining 70 mg. (8.5percent of theory) of 7-methoxy-2-(5-nitro-l-methyl-2-imidazolyl-methy1ene)-4-thiachromanone; m.p.

' N S 1 Calculated: 12.69 9.68 Found: 12.56 9.34

EXAMPLE 45 C i H N Calculated: 60.00 4.74 16.46 Found: 59.91 4.96 16.00

chloride in 8 ml. of pyridine. After dilution with 5 ml.

EXAMPLE 46 600 mg. (2.5 mmol) of 6-methanesulfonyloxy-ltetralone wasreacted as set forth in Example 41, but heated for 7 hours, and thenworked up as described therein, thus obtaining 250 mg. (27 percent oftheory) of 6-methanesulfony1oxy-2-(S-nitro-l-methyl-2-imidazolyl-methy1ene 1 -tetralone, m.p. 18 3185.

Calculated:

S 8. 0 Found: 8. 8

EXAMPLE 47 C H N Calculated: 60.19 4.38 14.04 Found: 60.19 4.75 13.76

EXAMPLE 48 365 mg. 2.5 mmol) of l-tetralone was reacted-as set forth inExample 41, but heated only for 2%hours, and then worked up as set forthin that example, thus obtaining 30 mg. (4.2 percent of theory) of2-(5-nitro-lmethyl-2-imidazolyl-methylene 1 -tetralone, m .p.

C H N Calculated: 63.59 4.63 14.83 Found: 64.01 4.97 14.48

EXAMPLE 49 l 1 g. (78 mmol) of 5-nitro-1-ethyl-imidazole was heated with11.7 g. of paraformaldehyde in 57 ml. of dimethyl sulfoxide in a sealedtube for 48 hours to 1 10. After the volatile components had beendistilled off at 1 mm. Hg and a bath temperature of the residue wasrecrystallized twice from benzene, thus producing 5.1 g.v (38 percent oftheory) of 5-nitro-l-ethyl-2- hydroxymethyl-imidazole; m .p. 10 1 1 02.

3.42 g. (20 mmol) of this compound was boiled in l 13 ml. of benzenewith 15 g. of lead tetraacetate for 8 hours. After cooling, filtering,washing the benzenic solution neutral, and drying the same, the productwas evaporated under a vacuum, thus obtaining 2.37 g. (70 percent oftheory) of 5-nitro-l-ethyl-2-imidazolyl aldehyde in the form of an oil.

424 mg. (2.5 mmol) of this compound was reacted with 370 mg. (2.5 mmol)of S-hydroxy-l-indanone, as set forth in Example 7. The crude productwas digested with hot ethanol, thus producing mg. (17 percent of theory)of 5-acetoxy-2-(5-nitro-l-ethyl-2- imidazolyl-methylene l -indanone,m.p. 225 -227.

c H N I Calculated: 59.82 4.43 12.32 Found: 59.50 4.30 12.38

EXAMPLE 50 3.66 g. (20 mmol) of 5-nitro-1-a1lyl-2-hydroxymethylimidazolewas treated with lead tetraacetate and worked up as described in Example49, thus btaining 2.7 g. (74 percent of theory) of -nitro-l-allyl-2-imidazolyl aldehyde in the form of an oil.

443 mg. (2.5 mmol) of this compound was reacted with 370 mg. (2.5 mmol)of S-hydroxy-l-indanone as set forth in Example 7. The crude product wasrecrystallized from ethanol, thus producing 18 mg. (2 percent of theory)of 5-acetoxy-2-(5-nitro-la1lyl-2- imidazolyl-methylene 1 -indanone, m.p.l88191.

C H N Calculated: 61.19 4.28 11.89 Found: 61.62 4.00 12.23

EXAMPLE 51 300 mg. (2.5 mmol) of acetophenone was reacted and worked upas described in Example 41; yield: 335 mg. (52 percent of theory) of2-(5-nitro-1-methy1-2- imidazolyl-methylene)-acetophenone, m.p. 202.

C H N Calculated: 60.70 4.31 16.34 Found: 60.47 4.27 16.33

EXAMPLE 52 340 mg. (2.5 mmol) of 4-hydroxyacetophenone was reacted andworked up as set forth in Example 41. Yield: 270 mg. (40 percent oftheory) of 4-hydroxy-2- (S-nitro- 1 -methy1-Z-imidazolylmethyleneacetophenone, m.p. 290.

acetophenone was reacted and worked up as described in Example 41.Yield: 406 mg. (45 percent of theory) of 4 2-acetoxyethoxy )-2-(5-nitrol methyl-2- imidazolyl-methylene )-acetophenone, m.p. 163.

Calculated: 56.82 4.77 1 1.70

Found: 57.10 5.18 11.68

EXAMPLE 54 405 mg. of 7-methoxyl-indanone was reacted and worked up asset forth in Example 10. Yield: 191 mg. (26 percent of theory) of7-methoxy-2-(5-nitro-lmethyl-2-imidazolyl-methylene l -indanone; m.p.273-282.

c H N Calculated: 60.19 4.38 14.04 Found: 59.63 4.57 13.81

EXAMPLE 55 570 mg. of 5-hydroxy-2-(5-nitro-l-methyl-2-imidazolylmethylene)-1-indanone was mixed in 10 m1.

of pyridine with 764 mg. of p-toluenesulfonyl chloride. After allowingthe reaction mixture to stand for 1 hour at 20 and for 1 hour at 100,it' was mixed with ethanol, cooled, and vacuum-filtered, thus obtaining707 mg. n

(64 percent-of theory) of 5-p-toluenesu1fonyloxy-2-(5- nitrol-methy1-2-imidazolyl-methylene 1 -indanone, m.p. 221 .5224.

N 5 Calculated: 9.56 7.30 Found: 9.88 7.10

EXAMPLE 56 4.8 g. of 5-nitro-1-( 2-benzoy1oxyethyl)-imidazole was heatedwith 2.76 g. of paraformaldehyde in 16.8 ml. of dimethyl sulfoxide in asealed tube at 1 10 for 48 hours. Evaporation under vacuum andrecrystallization from benzene yielded 2.77 g. (52 percent of theory) of5-nitro-2-hydroxymethyl-l-(2-benzoyloxyethyl)- imidazole, m.p. l36-l39.

5.84 g. of this compound was treated with lead tetraacetate and workedup, as described in Example 49. Yield: 3.95 g. (68 percent of theory) of5-nitro-l-(2- benzoyloxyethyl)-2-imidazolyl aldehyde, m.p. 113-11 4.

772 mg. of this compound was reacted with 370 mg. ofS-hydroxy-l-indanoneas described in Example 10 (except that the heatingstep was conducted for 4 hours), and worked up. Yield: 306 mg. (27percent of theory) of 5-acetoxy-2-[5-nitro- 1 -(2-benzoyloxyethy1)-2-imidazolyl-methylene1-l-indanone; m .p. l 86.5l 87.5.

C H N Calculated: 62.47 4.15 9.12 Found: 62.75 4.1 l 9.34

EXAMPLE 57 410 mg. of 4-thiachromanone was reacted and worked up as setforth in Example 41, thus obtaining 122 mg. (12 percent of theory) of3-( S-nitro-l-methyl- Z-imidazolyl-methylene)-4-thiachromanone l H SOm.p. l89/l90-193.

. C H N s Calculated: 42.10 3.28 10.53 16.04 Found: 42.54 3.53 10.4215.69

1-1 SO -Free Compound: Melting point: 176178.

N S Calculated: 13.95 10.64 Found: 13.47 10.44

EXAMPLE 58 555 mg. of 5-hydroxy-6,7-dimethoxy-l-tetralone was reactedand worked up as described in Example 41, thus obtaining 116 mg. (13percent of theory) of 5- hydroxy-6,7-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)- l -tetralone; m.p. 246248.

c H N Calculated: 56.82 4.77 1 1.70 Found: 56.79 4.99 11.36

EXAMPLE 59 70 mg. of 7-chloro-4,6-dimethoxy-3-benzofuranone was reactedas described in Example (except that the heating step is conducted at100 for 2% hours), and worked up. Yield: 353 mg. (39 percent of theory)of 7-chloro-4,6-dimethoxy-2-(S-nitro-1-methyl-2- imidazolyl-methylene)-3-benzofuranone; m.p. 295.

. N Calculated: 1 Found: 1

EXAMPLE 60 473 mg. of S-acetylamino-l-indanone was reacted and worked upas set forth in Example 57, thus obtaining 193 mg. (24 percent oftheory) of 5-acety1amino-2- (S-nitrol -methyl-2-imidazolylmethylene l-indanone,

m.p. 275 2s5.

C H N Calculated: 58.89 4.33 17.17 Found: 58.66 4.63 17.28

EXAMPLE 61 340 mg. (1 mmol) of 6-acetylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1tetralone was boiled in 8 ml. of ethanoland 4 ml. of concentrated hydrochloric acid for 2 hours. After coolingand vacuum-filtering, 169 mg. (56 percent of theory) of 6-amino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-ltetralone; m.p. 295.

C H N Calculated: 60.39 4.74 18.78 Found: 60.20 5.06 19.22

EXAMPLE 62 403 mg. of 6-amino-1-tetralone was reacted and worked up asdescribed in Example 41. Yield: 1 mg. 15 percent of theory) of6-amino-2-(5-nitro-l-methyl- 2-imidazolyl-methylene)-l-tetralone, m.p.295.

EXAMPLE 63 435 mg. of 5,7-dimethyl-l-tetralone was reacted and worked upas set forth in Example 41, thus obtaining 179 mg. (23 percent oftheory) of 5,7-dimethyl-2-(5- nitrol -methyl-2-imidazolylmethylene l-tetralone, m.p. 228229.

C H N Calculated: 65.59 5.51 13.50 Found: 65.51 5.73 13.46

EXAMPLE 64 568 mg. of 4-bromo-7-hydroxy-l-indanone was reacted asdescribed in Example 57. The product was digested with water andrecrystallized from acetonitrile. Yield: 318 mg. (32 percent of theory)of 4-bromo-7-acetoxy-2-( 5-nitrol -methyl-2-imidazolylmethylenel-indanone; m.p. 24825 1.

N Br Calculated: 10.35 19.67 Found: 10.32 19.96

EXAMPLE 65 690 mg. of sodium, 4.44 g. of S-hydroxy-l-indanone,

and 7.5 g. of 2-bromoethanol were boiled .for 48 hours with a spatulatip amount of potassium iodide in 40 ml. of alcohol. After the solventhad been removed by evaporation under vacuum, the residue was shakenwith 50 ml. of water and 50 ml. of ethyl acetate. The thus-producedprecipitate was vacuum-filtered and recrystallized from ethyl acetate,thus obtaining 900 mg. 16 percent of theory) of 5-(2-hydroxyethoxy- 1-indanone,.m.p. 121/ 122-127.

480 mg. of 5-(2-hydroxyethoxy)-l indanone was reacted and worked up asdescribed in Example 57.

- Yield: 145 mg. (16 percent of theory) of 5-(2-acetoxyethoxy )-2-( 5-nitrol -methyl-2-imidazolylmethylene 1 -indanone, m.p. 2 1 2/2 1 52 16.

C H N Calculated: 58.22 4.62 l 1.32 Found: 57.33 4.65 11.77

EXAMPLE 66 490 mg. of 5-chloro-4,6-dimethyl-3-benzofuranone was reactedas set forth in Example 57. By recrystallizing the product fromtetrahydrofuran, after digesting the product with water, 65 mg. (8percent of theory) of 5-chloro-4,6-dimethyl-2-( 5-r1itrol-methyl-2-imidazolyl-methylene)-3-benzofuranone was obtained; m.p. 265-27 1.

N C1 Calculated: 12.59 10.63 Found: 12.14 10.61

EXAMPLE 67 c H N Calculated: 61.74 5.18 11.38 Found: 61.80 5.46 10.81

EXAMPLE 68 455 mg. of thioindoxyl-l ,l-dioxide was reacted as set forthin Example 7. After cooling the reaction mixture,

filtering same off from sodium acetate, and mixing the filtrate withwater, a precipitate was obtained which was recrystallized fromacetonitrile. 33 mg. (4 percent theory) of2-(5-nitro-l-methyl-2-imidazolylmethylene)-thioindoxyll l-dioxide wasobtained, m.p. 288.

N S Calculated: 13.15 10.04 Found: 12.83 9.75

EXAMPLE 69 574 mg. (2 mmol) of 2-(5-nitro-1-methyl-2- theory) of2-(5-nitrol -methyl-2-imidazolylmethylene )-thioindoxyl- 1 -oxide; m.p.256.

N 8 Calculated: 13.85 10.56 Found: 14.06 10.69

EXAMPLE 70 638 mg. of -(2-dimethylaminoethoxy)-l-indanone,hydrochloride, was reacted as described in Example 7. After mixing thereaction mixture with water, it was extracted with chloroform. Theevaporated chloroform extract was taken up in methanol and mixed withether. After filtering, the filtrate was evaporated to dryness, and .theresidue was dissolved in 25 ml. of 2N hydrochloric acid. After thehydrochloric phase had been washed with ether and ethyl acetate, it wasmade alkaline with 2N sodium hydroxide solution, and extracted withchloroform. The residue of the evaporated chloroform extract was dilutedwith methanol and ether; by vacuum-filtering, 4.7 mg. (0.5 percent oftheory) of5-(2-dimethylarninoethoxy)-2-(5-nitro-lmethyl-Z-imidazolyl-methylene)-l-indanonewas obtained, m.p. 223-225.

The structure was confirmed by the mass spectrum, exhibiting intensivepeaks at 356 (M) and 58 [Cl-l 3)2]- EXAMPLE 71 662 mg. of5-methoxy-2-(5-nitro-l-methyl-2- imidazolylmethylene)-4-thiachromanonewas mixed in 50 ml. of glacial acetic acid with 0.5 ml. of 30 percenthydrogen peroxide. After agitation of the reaction mixture for 24 hoursat 20, 0.5 ml. of 30 percent hydrogen peroxide was added thereto, andafter another 24 hours at 20, a further 0.5 ml. of hydrogen peroxide wasintroduced. After 72 hours at 20, the reaction mixture was filtered, andthe precipitate was recrystallized from acetonitrile. Yield: 259 mg. (30percent of theory) of 5-methoxy-2-( 5 -nitrol-methyl-2-imidazolylmethylene )-4-thiachromanonel -oxide; m.p. 241/42-245.

Calculated: 12.10 9.23

Found: 12.05 9.33

EXAMPLE 72 ously with 12 ml. of dimetliyl sulfate and 6.75 ml. of 50percent sodium hydroxide solution. After cooling, the reaction mixturewas vacuum-filtered and the precipitate triturated with ether.- Theether filtrate resulted, after evaporation, in 3 g. of substance whichwas chromatographed over a silica gel column (150 g.) with petroleumether/ethyl acetate. First, 473 mg. of 6- dimethylamino-l-tetralone wasobtained, m.p. 6667, and then 1.21 g. of 6-methylamino-l-tetralone wasproduced, m.p. 93-94.'

473 mg. of 6-dimethylamino-l-tetralone was reacted as described inExample 41 thus obtaining 207 mg. (25 percent of theory) of6-dimethylamino-2-(5-nitro-lmethyl-2-imidazolylmethylene)-l-tetralone,m.p. 239/46-B49.

c H N Calculated: 62.57 5.57 17.17 Found: 62.50 5.73 16.98

EXAMPLE 73 46 mg. of sodium was dissolved in 10 ml. of alcohol,

and 220 mg. (2 mmol) of l-methyl-2-imidazolyl aldehyde, as well as 324mg. (2 mmol) of S-methoxy-lindanone were added thereto. After agitatingfor onehalf hour under a nitrogenatmosphere, the solution was pouredinto 20 ml. of water, and the crystals were vacuum-filtered. Yield: 258mg. (50 percent of theory) of 5-methoxy-2-(1-methyl-2-imidazolyl-methylene)-1- indanone, m.p. 258-259. 300 mg. ofthis compound was mixed in 1.6 ml. of nitric acid (sp. gr. 1.4) at 4with 1.6 ml. of concentrated sulfuric acid. The reaction mixture wasboiled for 2 hours under reflux, cooled to 20, and poured into icewater. Vacuum-filtering resulted in a mixture of substances, from which40 mg. of5-methoxy-2-(5-nitro-1-methyl-2-imidazolylmethylene)-l-indanone (11percent of theory), m.p. 256-259, was obtained by preparative thin-layerchromatography.

EXAMPLE 74 370 mg. (2.5 mmol) of S-hydroxy-l-indanone was treated andworked up as described in Example 41.

Yield: 450 mg. of 5-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone (63 percent of theory), m.p. 292.

EXAMPLE 75 5.4 g. (14.5 mmol) of 5-(2-acetoxyethoxy)-2-(5- nitrol-methyl-2-imidazolyl-methylene 1 -indanone was boiled for 2 hours in ml.of ethanol and 59 ml. of concentrated hydrochloric acid. After coolingthe reaction mixture, it was vacuum-filtered. Yield: 3.] g. (65 percentof theory) of 5-(2-hydroxyethoxy)-2-(5 nitrol-methyl-2-imidazolyl-methylene l -indanone, m.p. 258.

C H N Calculated: 58.36 4.60 12.76 Found: 58.05 4.85 12.29

I 23 EXAMPLE 76 625 mg. (1.92 mmol) of-acety1amino-2-(5-nitro-lmethyl-2-imidazolyl-methylene l -indanone wasboiled for 2 hours in 15.3 ml. of ethanol and 7.7 ml. of concentratedhydrochloric acid. Cooling, vacuum-filtering, and digesting in hot waterand then in hot ethanol resulted in 454 mg. (83 percent of theory) of 5-amino-2-( S-nitro- 1 -methyl-2-imidazolyl-methylene 1- indanone, m.p.292.

C H N Calculated: 59.14 4.26 19.71 Found: 59.14 4.38 19.47

EXAMPLE 77 300 mg. (2.5 mmol) of acetophenone was reacted as set forthin Example 7. After cooling, the reaction mixture was filtered to removesodium acetate and the filtrate mixed with 5 ml. of water.Vacuum-filtering resulted in 53 mg. (8 percent of theory) of2-(5-nitro-1- methy1-2-imidazolyl-methylene)-acetophenone, m.p. 202.

EXAMPLE 78 415 mg. (2.5 mmol) of 5,6-dihydroxy-l-indanone was treatedand worked up as described in Example 41. Recrystallization fromdimethylformamide-methanol resulted in 250 mg. (33 percent of theory) of5,6- dihydroxy-2-(5-nitro-1-methyl-2-imidazolylmethylene l-indanone,m.p.: above 290.

c 11 N Calculated: 55.81 3.68 13.95 Found: 55.38 4.05 13.77

EXAMPLE 79 520 mg. (2.5 mmol) of 4-fluoro-7-chloro-3-methy1- l-indanonewas treated as set forth in Example 7, except that the reaction mixturewas allowed to stand for 2% hours at 100. After cooling, the mixture wasmixed with methanol, the crystals were vacuum-filtered, digested in hotwater, and recrystallized from acetonitrile. Yield: 103 mg. (12 percentof theory) of 4-f1uoro-7-chloro-3-methyl-2(5-nitro-1-methyl-2-imidazolyl-methylene)- 1 -indanone, m.p. 225.

C H N Cl Calculated: 53.67 3.31 12.52 10.56 Found: 53.86 3.65 12.6210.30

EXAMPLE 80 375 mg. (2.5 mmol) of 6-hydroxy-3-benzofuranone was treatedand worked up as described in Example 41. Yield: 127 mg. (18 percent oftheory) of 6-hydroxy-2- 5 -nitro-1-methyl-2-imidazolyl-methylene)-3-benzofuranone'; m.p. above 290.

EXAMPLE 81 2.07 g. of sodium was dissolved in 12.0 ml. of ethanol, and14.6 g. (90 mmol) of 6-hydroxy-l-tetralone, 22.5 g. of 2-bromoethanol,and 0.4 g. of potassium iodide were added to the reaction-mixture. Afterboiling for 48 hours under a nitrogen atmosphere, the reaction mixturewas evaporated to dryness under a vacuum, mixed with 200 ml. of water,and extracted with ethyl acetate. The ethyl acetate solutions werewashed with 1N hydrochloric acid and water, dried, filtered, andconcentrated to dryness. Dilution of the residue with ether resulted in14.7 g. (79 percent of theory) of 6-(2- hydroxyethoxy)-l-tetralone, m.p.89-91.

C H Calculated: 69.89 6.85 Found: 69.62 7.00

515 mg. (2.5 mmol) of this compound was reacted and worked up as setforth in Example 41. Recrystallization from dimethylforrnamide yielded215 mg. (22

percent of theory) of 6-2-acetoxyethoxy)-2-(5-nitro-1-methyl-2-imidazoly1-methylene 1 -tetra.lone, 1 68.

C H N Calculated: 59.21 4.97 10.91 F ound: 59.68 5.08 10.69

EXAMPLE 82 N Calculated: 17.94 Found: 17.89

EXAMPLE 83 388 mg. (2.5 mmol) of 7-hydroxy-4-chromanone was treated andworked up as described in Example 41. Yield: 40 mg. (5 of theory) of7-hydroxy-3-(5nitro-lmethyl-2-imidazolyl-methylene)-4-chromanone, m.p.above 290.

C H N Calculated: 55.81 3.68 13.95 Found: 55.79 3.68 13.55

EXAMPLE 84 410 mg. (2.5 mmol) of 4-isothiachromanone was treated andworked up as set forth in Example 41. Yield: 156 mg. (21 percent oftheory) of 3-(5-nitro-lmethyl-2-imidazolyl-methylene)-4-isothiachromanone, m.p. 210.

N S Calculated: 13.95 10.64 Found: 13.48 10.79

EXAMPLE 85 2 g. (8.8 mmol) of Smitro-l-(2-acetoxyethyl )-2- imidazolylaldehyde and 1.43 g. (8.8 mmol) of methoxy-l-indanone were leftin 8.8ml. of acetic anhydride with 1.23 g. of anhydrous sodium acetate for 8hours at 100. After cooling, vacuum-filtering, and

- digestion of'the precipitate with hot water, 0.84 g. (26

percent of theory) of 5-methoxy-2-[5-nitro-1-(2-acetoxyethyl)-2-imidazolyl-methylene]-l-indanone was obtained, m.p. 190.

Calculated: 58.22 4.62 11.32 Found: 57.84 4.59 11.43

EXAMPLE 86 500 mg. (1.35 mmol) of 5-methoxy-2-[5-nitro-l-(2-acetoxyethyl )-2-imidazolylmethylene]-l-indanone was boiled in 10.8 ml.of ethanol and 5.4 ml. of concentrated hydrochloric acid for 2 hours.Cooling, mixing with 5 ml. of water, and vacuum-filtering resulted in388 mg. (87 percent of theory) of 5-methoxy-2-[5- nitrol 2-hydroxyethyl)-2-imidazolyl-methylene l indanone, m.p. 229.

C H N Calculated: 58.36 4.60 12.76 Found: 57.72 4.83 12.94

EXAMPLE 87 264 mg. (2 mmol) of l-indanone was reacted withlmethyl-2-imidazolyl aldehyde as described in Example 73, yielding 325mg. (72 percent oftheory) of 2-(1- methyl-2-imidazolyl-methylene l-indanone, m.p. l93l95. 300 mg. of this compound was nitrated asdescribed in Example 73. Yield afterpreparative layer chromatography: 17mg. (4 percent of theory) of 2-(5- nitro- 1 -methyl-2-imidazolyl-methylene 1 -indanone, m.p. 250-25l. 4

EXAMPLE 88 440 mg. (2.5 mmol) of 7-hydroxy-3,4-dimethyl-l-indanone wastreated and worked up as described in Example 41. Recrystallization fromdimethylformamide EXAMPLE 90 343 mg. (1 mmol) of6-(2-hydroxyethoxy)-2-(5- Calculated: 8.45 6.45 Found: 9.04 6.12

EXAMPLE 91 -10 g. (0.07 mol) of dimethylaminoethyl chloridehydrochloride and 2.8 g. 0.07 mol) of NaOH were dissolved in 20 ml. ofwater, extracted with benzene, and the benzenic solution was dried overK CO under agitation for 48 hours.

1.2 g. (0.052 mol) of sodium was dissolved in 50 ml.

of ethanol; then, 8.1- g. (0.05 mol) of 6-hydroxy-1- tetralone was addedthereto. The freshly prepared solution of dimethyl aminoethyl chlorideand a spatula tip amount of K1 were added to this reaction solution. Thelatter was stirred for 20 hours under reflux, then decanted ofi from theprecipitated NaCl; the solution was concentrated, the residue was takenup in 11 0 and extracted with ethyl acetate. The organic phase was driedover Na SO and concentrated. The oily residue was dissolved in ether andmixed with ethereal HCl. The thus-precipitated solid product wasvacuum-filtered and recrystallized from isopropanol. Yield: 7.4 g. (55percent of theory) of 6-(2-dimethylaminoethoxy)-ltetralone,hydrochloride; m.p. l'73174.

. N Cl Calculated; 5.19 13.13 Found: 520 13.19

yielded 33 mg. (5 percent of theory) of 7-hydroxy-3,4- I

dim ethyl-2-( S-nitrol -methyl-2-imidazolylmethylene)-l-indanone, m.p.193195. The structure was confirmed by the mass'spectrum (the molecularpeak, for example, is at313).

EXAMPLE 89 3.76 g. (9.76 mmol) of 6-(2-acetoxyethoxy)-2-(5- nitrol-methyl-2-imidazolyl-methylene)- l -tetralone was boiled in 78 ml. ofalcohol and 39 ml. of concentrated hydrochloric acidfor 2 hours. Aftercooling, the reaction mixture was poured into 234 ml. of water, and theprecipitate was vacuum-filtered. Yield: 2.79 g. (83 percent of theory)of 6-(Z hydroxyethoxy)-2-(5-nitrol-methyl-2-imidazolyl-methylene l-tetralone, m.p. 229-232.

C H N Calculated: 59.47 5.00 12.24 Found: 59.88 5.27 12.30

673 mg. (2.5 mmol) of 6-( 2-dimethylaminoethoxy)- l-tetralone,hydrochloride, was reacted as described in Example 41. The reactionmixture was worked up by pouring same into 10 ml. of water,concentrating the reaction solution under vacuum almost to dryness, anddiluting the residue with methanol/ether, as well as subsequentvacuum-filtering. Yield: 280 mg. (24 percent 7 of theory) of-6-(2-dimethylaminoethoxy) 2(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone as the sulfate; m.p.l96/200204.

Calculated: 4 l 1.96 6.85 Found: 1 1.49 7.05

EXAMPLE 92 658 mg. (2 mmol) of 5-( 2-hydroxyethoxy )-2-(5- nitrol-methyl-2-imidazolyl-methylene l -indanone was boiled in ml. of thionylchloride for 1 hour under reflux. The reaction mixture was cooled, andthen concentrated to dryness under vacuum. The residue wasrecrystallized from dimethylformamide. Yield: 416 mg. (60 percent oftheory) of 5-(2-chloroethoxy)-2-(5- nitro- 1-methyl-2*imidazolyl-methy1ene l -indanone; m.p. 23 8/242246.

N C1 Calculated: 12.09 10.20 Found: 1 1.73 9.35

EXAMPLE 93 718 mg. (2 mmol) of 4'-(2-acetoxyethoxy)-2 (5- nitro- 1-methyl-2-imidazolyl-methylene )-acetophenone was boiled in 16 ml. ofethanol and 8 ml. of concentrated hydrochloric acid for 2 hours underreflux. Dur

. ing the boiling step, the substance was dissolved, and a newprecipitate was formed. The product was cooled and vacuum-filtered.Yield: 599 mg. (85 percent of theory) of 4 2-hydroxyethoxy)-2-( S-nitrol-methyl- 2-imidazoly1-methylene)-acetophenone,

hydrochloride; m.p. 204/207-2 10.

N Cl Calculated: l 1.90 9.96 Found: '1 1.80 9.89

EXAMPLE 94 N S Calculated: 8.91 6.80 Found: 8.98 6.71

' EXAMPLE 95 942 mg. (2 mmol) of 4-(2-p-toluenesulfonyloxyethoxy)-2(5-nitro-1-methyl-2-imidazolyl-methylene)- acetophenone wasdissolved in 4 ml. of absolute dioxane and, after the addition of 0.2ml. (2.3 mmol) of morpholine, heated for 2 hours to 100. The reactionmixture was evaporated to'dryness under vacuum. The

residue was taken up in 10 ml. ofethyl acetate and 5 ml. of water. Thewater phase was separated, and the ethyl acetate phase was washed oncewithwater (2 ml.), dried over MgSO4, and evaporated. The residue wasrecrystallizedfrom ethyl acetate. Yield: 436 mg. (56 percent of theory)of 4'-(2-morpholinoethoxy)-2- (5-nitrol-methyl-2-imidazolyl-methylene)-acetophenone; m.p. l60161.5.

C H N Calculated: 59.06 5.75 14.50 Found: 58.71 5.76 14.16

The product was dissolved in methanol and, by the addition of etherealhydrochloric acid, the hydrochloride of the compound was precipitated;m.p. 201 /205-BR206.

EXAMPLE 96 339 mg. (2.5 mmol) of 4-aminoacetophenone was reacted andworked up as described in Example 41. The crude product wasrecrystallized from acetonitrile. Yield:acetylamino-2(5-nitro-1-methyl-2-imidazolylmethy1ene)-acetophenon; m.p.222-225.

Calculated: 57.40 4.49 17.85

- Found: 56.90 4.96 18.42

EXAMPLE 97 1.39 g. (4.42 mmol) of4-acetylamino-2-(5-nitro-lmethyl-Limidazolyl-methylene )-acetophenonewas boiled under reflux in 35.4 ml. of ethanol and 17.7 ml. ofconcentrated hydrochloric acid for 2 hours. The reaction mixture wascooled and vacuum-filtered. Yield: 684 mg. (52 percent of theory) of4-amino-2- (S-nitro- 1 -methyl-2-imidazolyl-methylene acetophenone,hydrochloride; m.p. 210 (decomposition N Cl Calculated: 18.15 1 1.48Found: 17.60 10.44

EXAMPLE 9 8 375 mg. (2.5 mmol) of 4-methy1-3-hydroxyacetophenone wasreacted and worked up as set forth in Example 41. Yield: 387 mg. (54percent of theory) of 4"-methyl-3 -hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene )-acetophenone; m.p. 290.

. C H N Calculated: 58.53 4.57 14.62 Found: 58.22 4.83 14.48

EXAMPLE 99 380 mg. (2.5 mmol) of 3,4'-dihydroxyacetophenone was reactedand worked up as described in Example 41. Yield: 464 mg. (64 percent oftheory) of 3,4- dihydroxy-2-( S-nitrol -methyl-2-imidazolylmethylene)-acetophenone; m.p. 290.

C H N Calculated: 53.98 3.84 14.53 Founded: 53.87 4.15 14.08

EXAMPLE 100 450 mg. 2.5 mmol) of 2',4'-dimethoxyacetophenone was reactedand worked up as described in Example 41. Yield; 219 mg. (27 percent oftheory) of 2 ,4 '-dimethoxy2-( S-nitrol -methyl-2-imidazolyl-methylene)-acetophenone; m.p. l24-1 26.

C H N Calculated: 56.79 4.77 13.25

Found: 57.30 5.16 12.76

mg. (17 percent of theory) of 4- EXAMPLE 101 471 mg. (1 mmol) of 4-(2-p-toluenesulfonyloxyethoxy )-2-( S-nitrol-methyl-2imidazolyl-methylene acetophenone was dissolved in 2 ml. ofabsolute dioxane and heated, with the addition of 142 mg. (2 mmol) ofpyrrolidine, for 2 hours to 100. The reaction mixture was concentratedto dryness under vacuum, and the residue was taken up in 10 ml. of ethylacetate and 10 ml. of water. The aqueous phase was separated, and theethyl acetate phase was washed once with ml. of H 0, dried over MgSO andevaporated. The residue was recrystallized from isopropanol/water,dissolved in methanol, and precipitated with ethereal hydrochloric acid.Yield: 105 mg. (27 percent of theory) of 4-(2- pyrrolidinoethoxy)-2-(S-nitro- 1 -methyl-2-imidazolylmethylene)-acetophenone, dihydrochloride,m.p. 200-202.

N C1 Calculated: 12.64 16.00 Found: 12.19 15.58

EXAMPLE 102 200 g. of 6,7-dimethoxy-2-(5-nitro-l-methyl-2-imidazolyl-methylene)-3-benzofuranone, 105.34 g. of corn starch, 8.0 g.of white gelatin, 6.5 g. of talc, 0.1 12 g. of methyl p-hydroxybenzoate,and 0.048 g. of propyl p-hydroxybenzoate are mixed homogeneously andcompressed into tablets of 320 mg. in the usual manner in a tabletcompressing machine.

EXAMPLE 103 2 .0 g. of 6-hydroxy-2-( 5 -nitrol -methyl-2-imidazolylmethylene)-4-tetralone, 27.0 g. of lactose, 45.565 g. of cornstarch, 4.0 g. of talc, 1.4 g. of white gelatin, 0.024 g. of methylp-hydroxybenzoate, and 0.01 1 g. of propyl p-hydroxybenzoate are mixedhomogeneously and compressed into tablets of 80 mg. in the usual mannerin a tablet compressing machine.

- EXAMPLE 104 g. of 6-acetoxy-5-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-l-indanone, 60 g. of lactose, 4.9 g. of cornstarch, 800 mg. of magnesium stearate, 8 mg. of methylp-hydroxybenzoate, and 3.5 mg. of propyl p hydroxybenzoate are mixedhomogeneously and processed in the usual manner by compressing intovaginal tablets of 750 mg.

EXAMPLE 105 1 1.5 g. (.70 mmol) of diethylaminoethyl chloridehydrochloride and 2.8 g. (70 mmol) of NaOH were dissolved in ml. ofwater, extracted with benzene, and the benzenic solution was dried for48 hours under stirring, over potassium carbonate. 1.2 g. (52 mmol) ofsodium was dissolved in 50 ml. of ethanol, and then 7.4 g. (50 mmol) of5hydroxy-l-indanone was added thereto. The freshly prepared solution ofdiethylaminoethyl chloride and a spatula tip amount of potassium iodidewere added to this reaction solution. The reaction mixture was stirredunder reflux for 24 hours; then, the reaction mixture was evaporated todryness under vacuum, the residue was taken up in water, and extractedwith ethyl acetate. The organic phase was dried over magnesium sulfateand concentrated. The oily residue was dissolved in ether and mixed withethereal HCl. The'thus-precipitated solid product was vacuum-filtered.

Yield: 8.66 g. (61 percent of theory) of 5-.(2-'

diethylaminoethoxy)-l-indanone, hydrochloride; m.p. 173175.

5 67 mg. (2 mmol) of 5-(2-diethylaminoethoxy)- 1 -indanone,hydrochloride, and 310 mg. (2 mmol) of 5- nitro-l-methyl-2-imidazolylaldehyde were stirred in 2.04 ml. of glacial acetic acid and 0.121. ml.(2.2 mmol) of concentrated sulfuric acid for 6 hours at 100. Thereaction mixture was evaporated almost to dryness under vacuum, theresidue was diluted with methanol, and. the crystalline solid productwas vacuum-filtered. Yield: 334 mg. (35 percent of theory) of 5-(2-diethylaminoethoxy)-2-( 5-nitro- 1 -methyl-2-imidazolyl-methylene)-l-indanone, sulfate; m.p. 194-196.5. 1

EXAMPLE 106 9.6 g. mmol) of 5-(2-hydroxyethoxy)-l-indanone and 9.5 g.(50 mmol) of p-toluenesulfonyl chloride were stirred in 100 ml. ofpyridine for 1.5 hours at room temperature. The reaction mixture waspoured into 500 ml. of ice water, and the crystalline solid product wasvacuum-filtered. Yield: 12.2 g. of 5- (2-p-toluenesulfonyloxyethoxy l-indan0ne (70 percent oftheory); m.p. 94 C.

6.92 g. (20 mmol) of 5-(2-p-toluenesulfonyloxyethoxy)-l-indanone and5.68 g. '(80 mmol) of pyrrolidine were boiled under reflux in 200 ml. ofethanol for 3 hours. After evaporating to dryness under vacuum, thereaction product was taken up in water and 2H NaOH and extracted withethyl acetate. The organic phase was dried over MgSO and concentrated.The oily residue was dissolved in ether and mixed with ethereal HCl. Thethus-precipitated solid product was vacuum-filtered. Yield: 2.5 g. (45percent of theory) of 5-( 2-pyrrolidinoethoxy)- l -indanone,hydrochloride.

2.5 g. (8.9 mmol) of 5-(2-pyrrolidinoethoxy)-1-indanone, hydrochloride,and 1.38 g. (8.9 mmol) of 5- nitro-l-methyl-2-imidazoly1 aldehyde werereacted as described in Example and worked up.

Yield: 0.75 g. (18 percent of theory) of5-(2-pyrrolidinoethoxy)-2-(S-nitro-1-methyl-2-imidazolylmethylene)-1-indanone,sulfate; m.p. 224225.

EXAMPLE 107 EXAMPLE 108 1.38 g. (4 mmol) of 5'(2-p-toluenesulfonyloxyethoxy)-l-indanone and 1.6 g. (16 mmol) ofl-methylpiperazine were reacted in 40 ml. of ethanol and worked up, asdescribed in Example 106. Yield: 1. l 7 g.

(94 percent of theory) of 5-[2-(4-methylpiperazino)- ethoxy]1-indanone,hydrochloride; m.p. 234236.

1.09 g. (3.5 mmol) of 5-[2-(4-methylpiperazino)- ethoxy]-l-'indanone,hydrochloride and 0.543 g. (3.5 mmol) of S-nitro-l-methyl-2-imidazolylaldehyde were reacted and worked up as set forth in Example 105. Yield:0.55 g. (31 percent of theory) of 5-[2-(4-methylpiperazino )-ethoxy]-2-(5 -nitrol -methyl-2-imidazolylmethylene l -indanone, sulfate; m.p.206209.

EXAMPLE 109 1.73 g. (5 mmol) of 5-(2-p-toluenesulfonyloxyethoxy)-1-indanone and 1.75 g. (20 mmol) ofmorpholine were reacted in 30 ml. of ethanol and worked up, as

EXAMPLE 1 10 1.38 g. (4 mmol) of5-(2-p-toluenesulfonyloxyethoxy)-l-indanone and 1.58 g. (16 mmol) ofperhydrozepine were reacted in 40 ml. of ethanol and worked up, asdescribed in Example 106. Yield: 0.67 g. (54 percent of theory) of5-[2-(l-perhydroazepinyD- ethoxy1- l -indanone, hydrochloride; m.p.177-l 79.

618mg. (2 mmol) of 5-[2-(l-perhydroazepinyl)- ethoxy]-l-indanone,hydrochloride, and'3l0 mg. (2 mmol) of S-nitro-l-methyl-2-imidazolylaldehyde were reacted and worked up as described in Example 105. Yield:210 mg. (21 percent of theory) of5-[2-(1-perhydroazepinyl)-eth0xy]-2-(S-nitro-1-methy1-2-imidazolyl-methylene l -indanone, sulfate; 212-2l4.

4.92 g. (33.3 mmol) of 4-hydroxyl-l-indanone was reacted withdimethylaminoethyl chloride and worked up, as set forth in Example 105.Yield: 4.4 g. (52 percent of theory) of 4-(2-dimethylaminoethoxy)-l-indanone, hydrochloride; m.p. 184l 86.

637 mg. (2.5 mmol) of 4-(2-dimethylaminoethoxy)- l-indanone,hydrochloride, and 388 mg. 2.5 mmol) of S-nitro-l-methyl-2-imidazolylaldehyde were reacted and worked up as described in Example 105. Yield:

750 mg. (66 percent of theory) of 4-(2-dimethylaminoethoxy)-2-(S-nitro-1-methyl-2-imidazolyl-methylene)-l-indanone, sulfate; m.p.- 225-227.

EXAMPLE 112 5.44 g. (37 mmol) of S-amino-l-indanone in 25 ml. of waterwas mixed dropwise at 80 simultaneously with 36 ml. of dimethyl sulfateand 15.5 g. of NaOH in 60 EXAMPLE 1 13 19.27 g. (93.5 mmol) of6-(2-hydroxyethoxy)-1- tetralone was reacted with 19.5 g. (102.85 mmol)of ptoluenesulfonyl chloride and worked up, as described in Example 106.Yield: 28.6 g. percent of theory) of6-(2-p-toluenesulfonyloxyethoxy)-l-tetralone; m.p. l06-'108.

3.6 g. (10 mmol) of 6-(2-p-toluenesulfonyloxyethoxy)-l-tetralone and3.48 g. (40 mmol) of morpholine were reacted and worked up as describedin Example 106. Yield: 1.73 g. (56 percent of theory) of 6-(2-morpholinoethoxy)-l-tetralone, hydrochloride; m.p. l94196.

1.87 g. (6 mmol) of 6-(2-morpholinoethoxy)-ltetralone, hydrochloride,and 0.93 g. (6 mmol) of 5- nitro-l-methyl-2-imidazolyl aldehyde wereagitated in 6.12 ml. of glacial acetic acid and 0.363 ml. (6.6 mmol) ofconcentrated sulfuric acid for 6 hours at After cooling, the reactionmixture was mixed with methanol and vacuum-filtered, thusproducing 1.04g. (34 percent of theory) of 6-(2-morpholinoethoxy)-2-(5-nitrol -rnethyl2-imidazolyl-methylene l -tetralone, sulfate; m.p. 223-224.

EXAMPLE 1 14 3.6 g. (10 lmmol) of6-(2-toluenesulfonyloxyethoxy)-l-tetralone and 2.84 g. (40 mmol) ofpyrrolidine were reacted and worked up as described in Example 106.Yield: 2.28 g. (77 percentof theory) of6-(2-pyrrolidinoethoxy)-l-tetralone, hydrochloride; m.p. 200203.

591 mg. (2 mmol) of 6-(2-pyrrolidinoethoxy)-1- tetralone, hydrochloride,and 310 mg. (2 mmol) of 5- nitro- 1 -methyl-2-imidazolyl aldehyde werereacted and worked up as described in Example 105. Yield: 216 6mg. (22percent of theory) of 6--(2-pyrrolidinoethoxy )-2- 5 -nitro-1-methyl-2-imidazolyl-methylene)- 1- tetralone, sulfate; m.p. 198-200.

EXAMPLE 1 15 473 mg. 2.5 mmol) of S-acetamino-l-indanone and 423 mg.(2.5 mmol) of S-nitro-1-ethyl-2-imidazolyl aldehyde were reacted as setforth in Example 7. The crude product was digested with methanol, thusobtaining 206 mg. (24 percent of theory) of 5-acetamino-2-(5 -nitrol-ethyl-2-imidazolyl-methylene l -indanone; m.p. 268-269.

33 EXAMPL 1 16 680 mg. (2 mmol) of5-acetamino-2-(5-nitro-lethyl-2-imidazolyl-methylene)-1-indanone wasreacted as described in Example 76, thus obtaining 550 mg. (92 percentof theory) of 5-amino-2-(5-nitro-l-2- imidazolyl-methylene)- 1-indanone; m.p. 290.

EXAMPLE 1 17 4.73 g. (25 mmol) of S-aceta'mino-l-indanone and 4.92 g. 25mmol) of S-nitro-l butyl-2-imidazolyl a1- dehyde were reacted and workedup as described in.Example 1 15. Yield: 2.19 g. (24 percent of theory)of 5- acetamino-Z-(S-nitro-l-butyl-2-imidazolylmethylene)-1-indanone;m.p. 240-242.

EXAMPLE 1 18 736 mg. (2 mmol) of5-acetamino-2-(5-nitro-lbutyl-2-imidazolyl-methylene)- 1 -indanone wasreacted as described in Example 76. Yield: 444 mg. (68 percent oftheory) of 5-amino-2-(5-nitro-l-butyl-2-imidazolylmethylene)-l-indanone, hydrochloride; m.p. 222.

EXAMPLE 1 l9 1 4.73 g. (25 mmol) of S-acetamino-l-indanone and 5.6 8 g.(25 mmol) of S-nitro-l-(2-acetoxyethyl)-2- imidazolyl aldehyde werereacted and worked up as set forth in Example 115. Yield: 2.27 g. (23percent of theory) of 5-acetamino-2-[5-nitro-l-(2-acetoxyethyl)-2-imidazolyl-methylene1-l-indanone; m.p. 227228 EXAMPLE 120 290 mg.(0.73 mmol) of 5-acetamino-2-[5-nitro-l-(2-acetoxyethy1)-2-imidazolyl-methylene]-1 -indanone was reactedasdescribed in Example 76. Yield: 166 mg.

] (2-pyrrolidinoethoxy)-acetophenone,

tered. Yield; 2.1 g. (61 percent of theory) of 4-(2-p-'toluenesulfonyloxyethoxy )-acetophenone; m.p. 82-84 1.67 g. (5 mmol) of4'-(2-p-toluenesulfonyloxyethoxy)-acetophenone and 1.42 g. mmol) ofpyrrolidine were reacted and worked up as described in Example 106.Yield: 0.7 g. (82 percent of theory) of 4- hydrochloride; m.p. 128-130.

674 mg. (2.5 mmol) of 4-(2-pyrrolidinoethoxy)- acetophenone,hydrochloride, and 388 mg. 2.5. mmol) of 5-nitro-l -methyl-2-imidazolylreacted and worked up as set forth in Example 105.

Yield: '503 mg. (43 percent of theory). of 4-(2-pyrrolidinoethoxy )-2-(S-nitro- 1 -methyl-2-imidazolyl- (73 percent of theory) of5-amino-2-[5-nitro-1-(2- hydroxyethyl)-2imidazolyl-methylene-]-1-indanone; m.p. 290-292.

EXAMPLE 121 353' mg. (1 mmol) of '4-(2-hydroxyethoxy)-2-(5nitro-1-methyl-2-imidazolyl-methylene)- acetophenone, hydrochloride, wasreacted and worked up as described in Example 92. Yield: 280 mg. (83per-- cent of theory) of4-(2-chloroethoxy)-2-(5-nitro-lmethyl-2-imidazolyl-methylene)-acetophenone;m.p.

EXAMPLE 122 264 mg. (0.55 mmol) of 4-(2-p-toluenesulfonyloxyethoxy )-2-(S-nitro- 1 -methyl-2-imidazolyl-methylene acetophenone was reacted with0.1 1 ml. (1.26 mmol) of morpholine and worked up, as described inExample 101. Yield: 236 mg. (97 percent of theory) of 4-(2-morpholinoethoxy )-2-( 5-nitrol-methyl-2-imidazolylmethylene)-acetophenone, hydrochloride; m.p.l86-l90.

EXAMPLE 123 1.8 g. (10 mmol) of 4-(2-hydroxyethoxy)- acetophe none and1.9 g. (10 mmol) of p-toluenesulfonyl chloride were stirred in 20 ml. ofpyridine for 2 hours at room temperature, then poured into 100 ml. ofwater, and the crystalline solid product wasvacuum-filmethylene)-acetophenone, sulfate; m.p. l 82-l 84.

EXAMPLE 124 EXAMPLE 125 5 g. (37 mmol) of 4'-aminoacetophenone ,in 25ml. of water was mixed dropwise at 80 simultaneously with 12 ml. ofdimethyl sulfate and 5.15 g. of NaOH in 20 ml. of water. After cooling,the reaction mixture was vacuum-filtered, and the precipitatewasrecrystallized from 70 percent aqueous methanol, thus obtaining 4.2

g. of 4'-dimethylarninoacetophenone percent of theory); m.p. l02l03.

408 mg. (2.5 mmol) of 4'- dimethylaminoacetophenone and 388 mg. (2.5mmol) of S-nitro-l-methyl-2-imidazolyl aldehyde were reacted and workedup as described in Example 41. Yield; 250 mg. (33 percent of theory) of4- dimethylamino-2-( S-nitro- 1 -methyl-2-imidazolylmethylene)-acetophenone; m.p. 2 37238.

EXAMPLE 126 147 mg. 1 mmol) of 5-amino-l-indanone and 228 mg. (1.2mmol)-of p-toluenesulfonyl chloride were boiledunder reflux in 2 m1. ofpyridine for 1.5 hours. After cooling, the reaction mixture was pouredinto 10 ml. of water, and the crystalline solid product wasvacuum-filtered; yield; 287 mg. of 5-p-toluenesulfonylamino-l-indanone.This product and 103 mg. (0.67 mmol) of S-nitrol -methyl-2-imidazolylaldehyde were reacted and worked up as described in Example 7. Yield:220 mg. percent of theory) of 5-ptoluenesulfonylamino-2-(5-nitro-1-methyl-2- imidazolyl methylene 1-indanone; m.p. 274275.

aldehyde were matic EXAMPLE 127 imidazolyl-methylene)-1 -indanone,sulfate; m.p. 208-2 1 c H N Calculated: 47.57 4.88 12.32 7.06 Found:47.46 5.00 12.50 6.91

The preceding examples can be repeated with similar success bysubstituting the generically and specifically described reactants and/oroperating conditions of this invention for those used in the precedingexamples;

From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

What is claimed is:

l. A compound of the formula wherein X is a saturated or unsaturatedhydrocarbon group containing one to five carbon atoms, or a free. or

,'8Ste1'lfi6d 2-hydroxyethyl group; Y and Z each are hydrogen atoms or,collectively, (a) CH (b) one of O, -S SO- and SO (c) a combination of(a) and one of (b); (d) CH CH or (e) CHA--, wherein A is CH;,, C H or CH R R and R each are H, alkyl of 1-5 carbon atoms, halogen, hydroxy,esterified hydroxy wherein the ester group is an ester of an aliphaticor aromatic carboxylic or sulfonic acid of one to 10 carbon atoms,etherified hydroxy wherein the ether group is alkoxy of one to fivecarbon atoms, alkyloxy or benzyloxy, and, additionally, R, can be alkylof l-5 carbon atoms substituted in the terminal position by halogen.hydroxy or esterified or ctherified hydroxy as defined hereinabove,

3. A compound of claim 2 wherein X is CH 4. A compound of claim 1wherein Yand Z collectively are CH 5. A compound of claim 1 wherein YandZ tively are CH CH 6. A compound of claim 1 wherein Y and Zcollectively are O.

7. A compound of claim 1 wherein Y and Z collectively are CH' S-.

8. A compound of claim 1 wherein Y and Z each are collec- 9. A compoundof claim 1 wherein at least one of R R and R is H.

10. A pharmaceutically acceptable acid addition salt of a compound ofclaim 1.

11. A compound of claim 4 selected from the group consisting of5-methoxy-2-( 5-nitro- 1 methy1-2- imidazolyl-methylene 1 indanone,5-ethoxy-2-( 5 nitro- 1 methyl-2-imidazolyl-methylene 1 -indanone,5-butoxy-2-(5-nitro-1-methy1-2-imidazolylmethylene 1 indanone, 4,5-dimethoxy-2-( 5 nitrolmethyl-2-imidazolyl-methylene)-1 indanone, 5methoxy-6-acetoxy-2-( S-nitro- 1 -methy1-2-imidazoly1- methylene l-indanone, 4-methoxy-2-(5-nitro-1- methyl-2-imidazo1yl-methylene 1-indanone, 5-a1lylox- I y-2-(5-nitro-1-methy1-2 imidazolyl-methylene)-1i11- amino, alkylamino or dialkylamino wherein alkyl is of one to fivecarbon atoms, or heterocyclic amino containing four to 14 carbon atoms,up to three rings and one to three N-, O and S heteroatoms, includingthe amino nitrogen atom, aminoalkoxy wherein alkoxy contains two to fivecarbon atoms and amino is an amino group as defined hereinabove, oracylamido wherein acyl is the acyl radical or analiphatic orarocarboxylic or sulfonic acid as defined hereinabove, and thepharmaceutically acceptable acid addition and quaternary ammonium saltsthereof.

2. A compound of claim 1 wherein X is alkyl containing one to fourcarbon atoms. 1

' imidazolyl-methylene 1 indanone,

danone, 5-benzoxy-2-( S-nitro- 1 methyl-Z-imidazolylmethylene 1indanone, 5,6-dimethoxy-2-(5-nitro-1-methyl-2imidazolyl-methylene)-l-indanone, 6- methoxy-5 -ace toxy-2-( 5nitro- 1 methyl-2-imidazolylmethylene)-1-indanone and7-methoxy-2-(5-nitro-1- methyl-2-imidazoly1-methylene)-1-indanone andthe pharmaceutically acceptable acid addition salts thereof. A

12. A compound of claim 1 1, 5-methoxy-6-acetoxy-2 -(5-nitro-1methyl-2-imidazolyl-methylene)-l-indanone. v

i 13. A compound of claim 11, 4,5-dimethoxy-2-(5-nitro-1-methyl-2-imidazo1y1-methylene)-l-indanone.

14. A compound'of claim 4 selected from the group consisting of4'-hydroxy-2-(5-nitro-1'-methy1-2- imidazolyl-methylene)-1-indanone,5-methoxy-6- hydroxy-2% S-nitro- 1 -methy1-2-imidazo1yl-methylenel-indanone, 5-hydroxy-2-(5-nitrol-methyl-Z- imidazolyl-methylene 1indanone, 7-hydroxy-2-( 5nitr'o-l-methy1-2-imidazolyl-methylene)-1indanone5-hydroxy-6-methoxy-2-(5-nitro-1-methyl-2- imidazolyl-methylene 1indanone, 4-chloro-7-hydroxy-2-(5-nitro-1methy1-2imidazolyhmethylene)-1-indanone,5,6-dihydroxy-2-(S-nitro-l-methy1-2- imidazoly1-methylene)- 1 -indanone,and 7-hydroxy-3,4-dimethyl-2-(5-nitro-1-methyl-2-imidazo1ylmethylcne)l-indanonc and thepharmaceutically acceptable acid addition salts thereof.

15. A compound of claim 4 selected from the group consisting of5'acetoxy-2-(5-nitro-1-methyl-2- 4-acetoxy-2-(5-nitro-1methyL2-imidazoly1-methylene)- l-indanone, 7-acetoxy-2-( 5-nitrol-methyl-2-imidazolylmethylene l indanone, 5-cinnamoyloxy-2-('5-nitro-1-methy1-2-imidazolyl-methylene)- 1 indanone, S-acetoxy-2-( 5-nitro- 1-ethyl-2-imidazo1yl-methylene 1 indanone,5-acetoxy-2-(5-nitro-1allyl-2-imidaz0ylmethy1ene)- 1 indanone,5-acetoxy-2-[5-nitro-1-(2- benzoyloxyethyl )-2-imidazoyl-methy1ene lindanone,4-bromo-7-acetoxy-2-(S-nitro-1-methy1-2-imidazoylmethylene)-l-indanone,-acetoxy-2-(5-nitro-l-butyl- 2-imidazolyl-methylene)l-indanone,4-chloro-7- acetoxy-2-( S-nitrol -methyl-2-imidazolyl-methylene)-l-indanone, 5-p-toluenesulfonyloxy-2-( S-nitro- 1methyl-2-imidazolyl-methylene)-l-indanone, 5- methoxy-2- S-nitrolZ-acetoxyethyl )-2-imidazoylmethylene]-1-indanone and5-methoxy-2-[5-nitro-l-(2-hydroxyethyl)-2-imidazoyl-methylene1-l-indanone and thepharmaceutically acceptable acid addition salts thereof.

16. A compound of claim 4 selected from the group consisting of5-chloro-2-(5-nitro-1-methyl'2- imidazolyl-methy1ene)-l-indanone, 2(5-nitro-lmethyl-2-imidazolyl-methylene)-l-indanone, 6- methyl-2-(S-nitrol -methyl-2-imidazolyl-methylene )-l -indanone, 6-chloro-2-(S-nitrol -methyl-2-imidazolylmethylene)-l-indanone,3-methyl-2-(5-nitro-l-methyl- 2-imidazolyl-methylene)-l-indanone,4-methyl-2-(5- nitrol -methyl-2-imidazolyl-methylene l -indanone,6-isopropyl-2-( S-nitrol -methyl-2-imidazolylmethylene)-l-indanone,4-chloro-2-(5-nitro-l-methyl- 2-imidazoyl-methylene)-l-indanone,3-phenyl-2-(5- nitrol -methyl'2-imidazolyl-methylene 1 -indanone, and4-fluoro-7-chloro-3-methyl-2-(S-nitrol -methyl-2- imidazolyl-methylene)-l -indanone and the pharmaceutically acceptable acid addition saltsthereof.

17. A compound of claim 4 selected from the group consisting of5-(2-ethoxyethoxy)-2-(5-nitro-l-methyl-2 -imidazolyl-methylene l-indanone, 5-(2-hydroxyethoxy)-2-(5-nitro-l-methyl-Z-imidazolylmethylene)-1-indanone,5-(2-chloroethoxy)-2-(5- nitrol -methyl-2-imidazolyl-methylene 1-indanone, and 5-( 2-acetoxyethoxy)-2-( 5-nitrol -methyl-2-imidazolyl-methylene)-l-indanone and the pharmaceutically acceptableacid addition salts thereof.

18. A compound of claim 4 selected from the group consisting of5-acetylamino-2-(5-nitro-l-methyl-Z- imidazolyl-methylene)-l-indanone,5-amino-2-(5- nitrol -methyl-2-imidazolyl-methylene l -indanone,5-acetamino-2-(5-nitro-l-ethyl-Z-imidazolylmethylene)-l-indanone,5-amino-2-(5-nitro-l'ethyl-2- imidazolyl-methylene)-l-indanone,5-acetamino-2-(5- nitro-l -butyl-2-imidazolyl-methylene)- 1 -indanone,5- amino-2-[5-nitro-1-(2-hydroxyethyl)-2-imadozylmethylene]-2-indanone,5-p-toluenesulfonylamino-Z-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-acetamino-2-[5-nitro-l-(2-acetoxyethyl)-2-imadazoyl-methylene1-l-indanone and 5-amino-2-(5-nitro-l-butyl-2-imidazolyl-methylene)-l-indanone and thepharmaceutically acceptable acid addition salts thereof.

19. A compound of claim 4, dimethylaminoethoxy)-2-(S-nitro-l-methyl-2-imidazolyl-methylene)-l-indanone and the pharmaceutically acceptableacid addition salts thereof.

20. A compound of claim 4,S-(Z-diethylaminoethoxy)-2-(5-nitro-l-methyl-2-imidazolyl-methylene)-1-indanoneand the pharmaceutically acceptable acid addition salts thereof.

21. A compound of claim 4, 5-(2-pyrrolidinoethoxy)-2-(5-nitro-l-methyl-2-imidazolylmethylene)-1-indanone and thepharmaceutically acceptable acid addition salts thereof.

22. A compound of claim 4, 5-(2-piperidinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-l-indanone and thepharmaceutically acceptable acid addition salts thereof.

23. A compound of claim 4, 5-[2-(4-methylpiperazino)-ethoxy ]2-(S-nitrol -methyl-2-imidazolylmethylene)-l-indanone and thepharmaceutically acceptable acid addition salts thereof.

24. A compound of claim 4, 5-(2-morpholinoethoxy)-2'-(5 -nitrol-methyl-2-imidazolyl-rnethyleney l indanone and the pharmaceuticallyacceptable acid addition salts thereof.

25. A compound of claim 4, 5-[2-(l-perhydroazepinyl)-ethoxy]-2-(5-nitro-1-methyl-2-imidazolylmethylene)-l-indanoneand the pharmaceutically acceptable acid addition salts thereof.

26. A compound of claim 4, dimethylaminoethoxy)-2-(5-nitro-l-methyl-2-imidazolyl-methylene )-1-indanone and the pharmaceutically acceptableacid addition salts thereof.

27. A compound of claim 4, 5-dimethylamino-2-(5- nitrol-methyl-2-imidazolyl-methylene)- l -indanone and the pharmaceuticallyacceptable acid addition salts thereof.

28. A compound of claim 5 selected from the group consisting of6-methoxy-2-(5-nitro-1-methyl-2- imidazolyl-methylene)-1-tetralone,6-acetylamino2-( 5 -nitro-1-methyl-2-imidazolyl-methylene)-l-tehalone,

6-methanesulfonyloxy-2-( S-nitrol -methyl-2- imidazolyl-methylene)- l-tetralone, 6-hydroxy-2-( 5-nitro-l-methyl-Z-imidazoyl-methylene)-1-tetralone, 2- (S-nitrol-methyl-2-imidazolyl-methylene l tetralone,5-hydroxy-6,7-dimethoxy-2-(S-nitro-lmethyl-2-imidaz0lyl-methylene)-1-tetralone,6-amino- 2-( S-nitrol -methyl-2-imidazoyl-methylene l tetralone, 5,7-dimethyl-2-( S-nitrol -methyl-2- imidazolyl-methylene)-l-tetralone,6-dimethylamino- 2-( 5-nitrol -methyl-2-imidazolyl-methylene ltetralone, 6-(2-acetoxyethoxy)-2-(S-nitro-l-methyl-2-imidazolyl-methylene)-l-tetralone, 6-methylamino-2- (S-nitrol-methyl-2-imidazolyl-methylene l tetralone, 6-( 2-hydroxyethoxy)-2-(5'-nitro- 1 -methyl-2- imidazolyl-methylene 1 -tetralone, and 6-(2-ptoluenesulfonyloxyethoxy )-2-( S-nitrol -methyl-2-imidazolyl-methylene)-l-tetralone and the pharmaceutically acceptableacid addition salts thereof.

29. A compound of claim 5, dimethylaminoethoxy)-2-(S-nitro-l-methyl-Z-imidazolyl-methylene )-l-tetra10ne and the pharmaceutically acceptableacid addition salts thereof.

30. A compound of claim 5, 6-(2-morpholinoethoxy )-2-(5-nitrol-methyl-2-imidazolyl-methylene l tetralone and the pharmaceuticallyacceptable acid addition salts thereof.

31. A compound of claim 5,6-(2-pyrrolidinoethoxy)-2-(5-nitro-l-methyl-2-imidazolyl-methylene)-ltetraloneand the pharmaceutically acceptable acid addition salts thereof.

32. A compound of claim 6 selected from the group consisting of6-hydroxy-2-(5-nitro-l-methyl-2- imidazolyl-methylene)-3-benzofuranone,6,7- dimethoxy-2-( 5 -nitrol -methyl-2-imidazolylmethylene)-3-benzofuranone, 7-chloro-4,6-dimethoxy-2-( S-nitrol -methyl-2-imidazolyl-methylene )-3- benzofuranone, and5-chloro-4,6-dimethyl-2-(S-nitrov

2. A compound of claim 1 wherein X is alkyl containing one to fourcarbon atoms.
 3. A compound of claim 2 wherein X is CH3.
 4. A compoundof claim 1 wherein Y and Z collectively are -CH2-.
 5. A compound ofclaim 1 wherein Y and Z collectively are -CH2CH2-.
 6. A compound ofclaim 1 wherein Y and Z collectively are -O-.
 7. A compound of claim 1wherein Y and Z collectively are -CH2-S-.
 8. A compound of claim 1wherein Y and Z each are H.
 9. A compound of claim 1 wherein at leastone of R1, R2 and R3 is H.
 10. A pharmaceutically acceptable acidaddition salt of a compound of claim
 1. 11. A compound of claim 4selected from the group consisting of5-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-ethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-butoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,4,5-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-methoxy-6-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,4-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-allyloxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-benzoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5,6-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,6-methoxy-5-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanoneand 7-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone andthe pharmaceutically acceptable acid addition salts thereof.
 12. Acompound of claim 11,5-methoxy-6-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone.13. A compound of claim 11,4,5-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone.14. A compound of claim 4 selected from the group consisting of4-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-methoxy-6-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,7-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-hydroxy-6-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,4-chloro-7-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5,6-dihydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,and 7-hydroxy-3,4-dimethyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 15. A compound of claim 4 selected from the group consisting of5-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,4-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,7-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-cinnamoyloxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-acetoxy-2-(5-nitro-1-ethyl-2-imidazolyl-methylene)-1-indanone,5-acetoxy-2-(5-nitro-1-allyl-2-imidazoyl-methylene)-1-indanone,5-acetoxy-2-(5-nitro-1-(2-benzoyloxyethyl)-2-imidazoyl-methylene)-1-indanone,4-bromo-7-acetoxy-2-(5-nitro-1-methyl-2-imidazoyl-methylene)-1-indanone,5-acetoxy-2-(5-nitro-1-butyl-2-imidazolyl-methylene)-1-indanone,4-chloro-7-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-p-toluenesulfonyloxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-methoxy-2-(5-nitro-1-(2-acetoxyethyl)-2-imidazoyl-methylene)-1-indanoneand5-methoxy-2-(5-nitro-1-(2-hydroxyethyl)-2-imidazoyl-methylene)-1-indanoneand the pharmaceutically acceptable acid addition salts thereof.
 16. Acompound of claim 4 selected from the group consisting of5-chloro-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,6-methyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,6-chloro-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,3-methyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,4-methyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,6-isopropyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,4-chloro-2-(5-nitro-1-methyl-2-imidazoyl-methylene)-1-indanone,3-phenyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone, and4-fluoro-7-chloro-3-methyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 17. A compound of claim 4 selected from the group consisting of5-(2-ethoxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-(2-hydroxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-(2-chloroethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,and5-(2-acetoxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanoneand the pharmaceutically acceptable acid addition salts thereof.
 18. Acompound of claim 4 selected from the group consisting of5-acetylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-amino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-acetamino-2-(5-nitro-1-ethyl-2-imidazolyl-methylene)-1-indanone,5-amino-2-(5-nitro-1-ethyl-2-imidazolyl-methylene)-1-indanone,5-acetamino-2-(5-nitro-1-butyl-2-imidazolyl-methylene)-1-indanone,5-amino-2-(5-nitro-1-(2-hydroxyethyl)-2-imadozyl-methylene)-2-indanone,5-p-toluenesulfonylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone,5-acetamino-2-(5-nitro-1-(2-acetoxyethyl)-2-imadazoyl-methylene)-1-indanoneand 5-amino-2-(5-nitro-1-butyl-2-imidazolyl-methylene)-1-indanone andthe pharmaceutically acceptable acid addition salts thereof.
 19. Acompound of claim 4,5-(2-dimethylaminoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 20. A compound of claim 4,5-(2-diethylaminoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 21. A compound of claim 4,5-(2-pyrrolidinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 22. A compound of claim 4,5-(2-piperidinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 23. A compound of claim 4,5-(2-(4-methylpiperazino)-ethoxy)2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanoneand the pharmaceutically acceptable acid addition salts thereof.
 24. Acompound of claim 4,5-(2-morpholinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid addition saltsthereof.
 25. A compound of claim 4,5-(2-(1-perhydroazepinyl)-ethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptable acid additionsalts thereof.
 26. A compound of claim 4,4-(2-dimethylaminoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanone and the pharmaceutically acceptablE acid addition saltsthereof.
 27. A compound of claim 4,5-dimethylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-indanoneand the pharmaceutically acceptable acid addition salts thereof.
 28. Acompound of claim 5 selected from the group consisting of6-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-acetylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-methanesulfonyloxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-hydroxy-2-(5-nitro-1-methyl-2-imidazoyl-methylene)-1-tetralone,2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,5-hydroxy-6,7-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-amino-2-(5-nitro-1-methyl-2-imidazoyl-methylene)-1-tetralone,5,7-dimethyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-dimethylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-(2-acetoxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-methylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,6-(2-hydroxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone,and6-(2-p-toluenesulfonyloxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetraloneand the pharmaceutically acceptable acid addition salts thereof.
 29. Acompound of claim 5,6-(2-dimethylaminoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone and the pharmaceutically acceptable acid addition saltsthereof.
 30. A compound of claim 5,6-(2-morpholinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone and the pharmaceutically acceptable acid addition saltsthereof.
 31. A compound of claim 5,6-(2-pyrrolidinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-1-tetralone and the pharmaceutically acceptable acid addition saltsthereof.
 32. A compound of claim 6 selected from the group consisting of6-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-3-benzofuranone,6,7-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-3-benzofuranone,7-chloro-4,6-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-3-benzofuranone, and5-chloro-4,6-dimethyl-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-3-benzofuranone and6-acetoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-3-benzofuranoneand the pharmaceutically acceptable acid addition salts thereof.
 33. Acompound of claim 7 selected from the group consisting of7-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-4-thiachromanone,3-(5-nitro-1-methyl-2-imidazolyl-methylene)-4-thiachromanone, and5-methoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-4-thiachromanone-1-oxide and the pharmaceutically acceptable acid addition salts thereof.34. A compound of claim 1,2-(5-nitro-1-methyl-2-imidazolyl-methylene)-thioindoxyl.
 35. A compoundof claim 1,2-(5-nitro-1-methyl-2-imidazolyl-methylene)-thioindoxyl-1,1-dioxide. 36.A compound of claim 1,2-(5-nitro-1-methyl-2-imidazolyl-methylene)-thioindoxyl-1-oxide.
 37. Acompound of claim 1,3-(5-nitro-1-methyl-2-imidazolyl-methylene)-4-isothiachromanone.
 38. Acompound of claim 1 selected from the group consisting of3-(5-nitro-1-methyl-2-imidazolyl-methylene)-4-chromanone,7-acetoxy-3-(5-nitro-1-methyl-2-imidazolyl-methylene)-4-chromanone and7-hydroxy-3-(5-nitro-1-methyl-2-imidazoyl-methylene-4-chromanone and thepharmaceutically acceptable acid addition salts thereof.
 39. A compoundof claim 8 selected from the group consisting of2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,4''-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,4''-(2-acetoxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,4''-(2-hydroxyethoxy)-2-(5-nitro-1-methyl-2-imidazoyl-methylene)-acetophenone,4''-(2-p-toluenesulfonyloxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,4''-methyl-3''-hydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,3'',4''-dihydroxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,2'',4''-dimethoxy-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenoneand4''-(2-chloroethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenoneand the pharmaceutically acceptable acid addition salts thereof.
 40. Acompound of claim 8 selected from the group consisting of4''-acetylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone,4''-amino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone and4''-dimethylamino-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenoneand the pharmaceutically acceptable acid addition salts thereof.
 41. Acompound of claim 8,4''-(2-morpholinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone and the pharmaceutically acceptable acid addition saltsthereof.
 42. A compound of claim 8,4''-(2-pyrrolidinoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone and the pharmaceutically acceptable acid addition saltsthereof.
 43. A compound of claim 8,4''-(2-dimethylaminoethoxy)-2-(5-nitro-1-methyl-2-imidazolyl-methylene)-acetophenone and the pharmaceutically acceptable acid addition saltsthereof.
 44. A compound of claim 1 wherein X is saturated or unsaturatedalkyl of 1-5 carbon atoms, 2-hydroxyethyl, 2-benzoyloxyethyl, or2-alkanoyloxyethyl wherein alkanoyl is of 2-3 carbon atoms; R1 ishydrogen, halogen, alkyl of 1-5 carbon atoms, a hydroxy, alkanoyloxygroup of 2-3 carbon atoms, or saturated or unsaturated alkoxy group of1-5 carbon atoms; and R2 is hydrogen, halogen, alkyl of 1-5 carbonatoms, a hydroxy, alkanoyloxy of 2-3 carbon atoms, saturated orunsaturated alkoxy group of 1-5 carbon atoms, cinnamoyloxy,alkylsulfonyloxy group of 1-2 carbon atoms, p-toluenesulfonyloxy,benzyloxy, amino, alkanoylamino of 2-3 carbon atoms, benzoylamino,p-toluenesulfonylamino, monoamino or dialkylamino wherein alkyl is of1-2 carbon atoms, benzylamino or an alkoxy group of 2-4 carbon atomssubstituted in the terminal position by one of chlorine, hydroxy,alkanoyloxy of 2-3 carbon atoms, p-toluenesulfonyloxy, or wherein A andB each are hydrogen, or saturated or unsaturated alkyl of 1-5 carbonatoms, or A and B collectively with the N-atom are pyrrolidino,piperidino, morpholino, piperazino, or piperaziNo substituted on the4-position nitrogen atom by alkyl of 1-5 carbon atoms,hexa-methylenimino, heptamethylenimino or octamethylenimino, or acorresponding alkyleneimino group bridged directly or by lower alkylene.45. A compound of claim 44 wherein X and Y each are hydrogen.
 46. Acompound of claim 44 wherein X and Y each collectively are -CH2-.
 47. Acompound of claim 44 wherein X and Y each collectively are -CH2CH2-.